Gene Reports

Cancer-related genomic instability (GI) may cause genetic alterations in spermatozoa, implying health issues not only in cancer survivors, but also in their children [1, 2]. We therefore studied Loss of Y chromosome (LOY), considered as hallmark of GI [3-15], in spermatozoa and blood from survivors of childhood and testicular cancer (CC, TC), and controls (CTRL). We found that LOY was statistically significantly more frequent in spermatozoa from cancer survivors than in controls (Odds Ratio [OR]=2.2 for CC vs. CTRL and OR=2.4 for TC vs. CTRL). Furthermore, LOY was about an order of magnitude more prevalent in spermatozoa than in blood among 18-53-year-old males within all cohorts. Our findings suggest that LOY in spermatozoa might be a clinically useful marker of GI, reduced fertility and disease predisposition in males. Introducing LOY in spermatozoa as a biomarker opens a new research avenue into disease prevention and the causes and consequences of LOY.

BackgroundThe ability of TRAIL to specifically induce apoptosis in cancer cells makes it a promising candidate to be an effective chemotherapeutic drug. But resistance to TRAIL treatment is a major obstacle. Finding combinatorial therapies that make resistant tumors more susceptible to TRAIL is an effective preclinical approach. In this work, we investigated the possibility that pre-treatment of paclitaxel may promote apoptosis in TRAIL-resistant breast cancer cells. MethodsIn silico analysis was done to investigate the binding affinity between TRAIL receptors (DR5 and DCR2) and paclitaxel via docking and MD simulation. To check whether any non-lethal dose of paclitaxel can modulate the expression of TRAIL receptors, qPCR was done in paclitaxel treated breast cancer cells. Next, paclitaxel was pre-administered to TRAIL-resistant MCF7 and MDA-MB-453 human breast cancer cells followed by rhTRAIL treatment. Cell viability and survival was evaluated using the MTT assay and colony formation assay, respectively. Immunoblot for caspase-3 was performed to study apoptosis. The expression level changes of DR5 and DCR2 were analyzed post-treatment using qPCR and immunoblot assay. ResultsIn silico analysis showed that paclitaxel can bind with higher stability to DCR2 in comparison to DR5 thereby changing the preference of TRAIL molecules towards DR5. Next, in cell line experiments we observed that administering a non-lethal dose of paclitaxel to MDA-MB-231 and MCF7 breast cancer cells resulted in no significant cell death but led to an increase in DR5 and a decrease in DCR2 expression at both the transcript and protein levels. Furthermore, in TRAIL-resistant MCF7 and MDA-MB-453 cells, pre-treatment with paclitaxel followed by rhTRAIL administration induced significant cell death due to paclitaxel induced increase in DR5 as well as decrease in DCR2 expression at both the transcript and protein levels. Moreover, long term survival of MDA-MB-453 cells was significantly lower when pretreated with paclitaxel and exposed to rhTRAIL compared to control, paclitaxel alone or rhTRAIL alone group. ConclusionThus, our study uncovers a novel therapeutic strategy to overcome TRAIL resistance underscoring the clinical potential of using a non-lethal dose of paclitaxel to modulate TRAIL receptor dynamics. Future research should be aimed at exploring the potentiality of using paclitaxel-based combinatorial approaches in crafting effective TRAIL therapies.

Purpose This study aimed to evaluate the efficacy and safety of neoadjuvant chemotherapy (NAC) combined with the programmed death protein 1 (PD-1) inhibitor sintilimab versus NAC alone in patients with triple-negative breast cancer (TNBC). Materials and Methods In this retrospective cohort study, we collected clinical data from 61 patients with triple-negative breast cancer (TNBC) who received neoadjuvant therapy at The First Hospital of Lanzhou University between July 2024 and July 2025. These patients were divided into two groups: the neoadjuvant chemotherapy (NAC) plus sintilimab group (n=27) and the NAC-alone group (n=34). The primary endpoint was the pathological complete response (pCR) rate. Secondary endpoints included objective response rate (ORR), safety, and changes in tumor markers. Results The combination therapy group showed significantly higher ORR (85.2% vs. 58.8%) and pCR rates (59.3% vs. 32.4%) compared to the NAC alone group (both P<0.05). Post-treatment Ki-67 levels were also significantly lower in the combination group (P<0.05). The overall incidence of adverse events was comparable between groups (P>0.05), although leukopenia was more frequent with sintilimab (P<0.05). Conclusion In the neoadjuvant setting for TNBC, the addition of sintilimab to NAC significantly improves ORR and pCR rates, effectively reduces the tumor proliferation index Ki-67, and does not significantly increase the overall burden of adverse events. The combination regimen shows a manageable safety profile and demonstrates positive clinical value. Keywords Triple Negative Breast Cancer, Immunotherapy, Sintilimab, Combination neoadjuvant chemotherapy, Efficacy, Real-World data.

This study investigates the therapeutic potential of secretomes derived from Adipose-derived Mesenchymal Stem Cells (ADMSC-CM) and Limbal-derived Mesenchymal Stem Cells (LMSC-CM) against oxidative stress-induced damage in Retinal Pigment Epithelium (RPE-1) cells. RPE dysfunction, often triggered by oxidative stress, is a hallmark of various retinal degenerations. Here, we induced RPE-1 injury using H2O2 and evaluated the restorative effects of both MSC-conditioned media (CM). Our results demonstrated that both ADMSC-CM and LMSC-CM significantly enhanced cell viability and successfully reversed H2O2-induced G2/M phase cell cycle arrest. While oxidative stress triggered a pro-inflammatory response characterized by elevated IL-1{beta}, IL-6, and IL-10 expression, MSC-CM treatment, particularly ADMSC-CM, effectively modulated these levels and suppressed the p38 MAPK signaling pathway. Furthermore, MSC-CM reduced the Bax/Bcl-2 ratio, indicating an anti-apoptotic effect, and appeared to stabilize autophagic flux. To investigate the impact of oxidative-stress induced alterations in retinal pigment epithelial cells on angiogenesis, the effects of RPE-derived secreted factors on endothelial cell function were evaluated. Crucially, in terms of safety and secondary complications, neither secretome exhibited pro-angiogenic tendencies; instead, they significantly inhibited HUVEC migration and invasion compared to the H2O2 damaged group. These findings suggest that both ADMSC and LMSC secretomes provide a potent multi-targeted therapeutic effect, making them promising candidates for cell-free therapies in retinal diseases.

Alleles of ASIP gene (Agouti locus) in dogs determine a wide spectrum of coat colors, from red to black. Gain-of-function Ay allele is the most dominant in the range of known ASIP mutations: when all other genes affecting coat pigmentation are intact, presence of Ay allele results in red coat color. Loss-of-function a allele is the most recessive allele of this gene. When homozygous, it gives black coat color. Usually, dogs with Ay/a genotype have red coat, because a single copy of Ay allele is sufficient to fully compensate for the non-functional allele a, implying the complete dominance in this pair of alleles. However exceptions are known. In the Hungarian Puli breed there is a specific coat pigmentation type called fako. We investigated the genetic composition of fako dogs and found evidence that the dominance of the Ay allele over the a allele may be incomplete in these dogs. Analysis of the MC1R gene that interacts with ASIP in the hair pigmentation genetic cascade allowed us to find the variants that may be responsible for the incomplete dominance of Ay allele over a allele in Hungarian Puli dogs.

BackgroundConventional models of human ribosomal DNA (rDNA) array organization have historically depended on transcription-centric boundaries, partitioning the unit into a [~]13 kb rDNA transcription region and a monolithic [~]31 kb intergenic spacer (IGS). While our previous identification of Duplication Segment Units (DSUs) mapped these arrays based on an intuitive analysis of the microsatellite density landscape of the complete reference human genome, our present deep mining of this landscape has revealed a more accurate rDNA Gene Unit Pattern. Methods & ResultsIn this study, we conducted a deep mining analysis of our previously established microsatellite density landscape of the T2T-CHM13 assembly, focusing specifically on nucleolar organizing regions (NORs). We suggest a more accurate rDNA Gene Unit Pattern containing a (CTTT)n microsatellite aggregation ahead of the rDNA gene and a (CT)n microsatellite aggregation behind the gene, rather than a pattern featuring an IGS region inserted between two rDNA genes. ConclusionsA correct rDNA gene pattern of the human genome probably includes a (CTTT)n microsatellite aggregation ahead of the gene and a (CT)n microsatellite aggregation behind it, which possibly constitute cis- and trans-regulating regions; the (CTTT)n and (CT)n microsatellite aggregations may provide two different local stable DNA structures for regulatory protein binding.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and lacks effective therapies. The stimulator of interferon genes (STING) has been shown to both suppress and promote migration in various cancer types, but its role in TNBC remains unclear. To investigate this, we established STING-overexpressing murine TNBC cell lines and assessed their migratory and proliferative behavior. STING overexpression significantly suppressed cell migration without affecting cell proliferation. Furthermore, STING overexpression upregulated expression levels of Itgb1 and Itga6 significantly, but not Icam1, Cxcl3, Itgb2, Lama5, and Rhoa. These findings highlight the potential anti-migratory role of STING beyond immunomodulatory functions.

This study aimed to examine whether Humanin-G (HNG), a mitochondrial derived peptide with cytoprotective properties, could improve the retinal function and gene expression profiles after intraperitoneal injections to Royal College of Surgeons (RCS) rats with Retinal Pigment Epithelium (RPE) dysfunction and retinal degeneration. Starting at postnatal day 21 (p21), RCS rats received twice a week intraperitoneal injections of either Low Dose HNG (0.4 mg/kg), High Dose HNG (4mg/kg), or sham-saline for 1 or 4 weeks. Visual function was tested with full field scotopic & photopic electroretinography (ERG) and optokinetic testing (OKT) 1 and 4 weeks after first injection (WAFI). The rats were euthanized after the ERG and OKT (1 or 4 WAFI) and the dissected retinas and RPE were collected for RNA, cDNA and Quantitative Real-time PCR (qRT-PCR) analysis. The results of our study showed that high dose (4mg/kg) HNG at 4 WAFI was associated with the largest change in gene expression in the RPE and retina of treated animals, altering expression of genes involved in apoptosis, oxidative stress, inflammation and retinal/RPE function. Analysis of a and b waves from scotopic and photopic ERG showed no difference between either low or high dose of HNG and sham injection at 4 WAFI. However, at 4 WAFI, the visual acuity in rats treated with high dose HNG showed significant improvement as compared to the rats treated with low dose of HNG or saline. Most significantly, our findings support that HNG administered IP can modulate RPE/neuroretina cells and improve vision, thus may be a potential treatment for retinal degeneration diseases.

The MYC associated factor X (MAX) is the heterodimeric partner of the MYC paralogs (MYC, MYCN and MYCL). When deregulated, high level of the MYC paralogs contribute to all aspects of tumorigenesis and tumor growth. MAX can also heterodimerize with the MXD proteins, MNT and MGA. Heterodimerization and sequence specific DNA binding to the E-Box sequences at gene promoters is controlled by their heterodimerization with the MAX b-HLH-LZ. As a heterodimer with MAX, MYC proteins activate genes involved in cell metabolism, growth and proliferation whereas MXD proteins, MNT and MGA repress them. MAX can also bind to the E-Bos sequence as a homodimer. Being devoid of a transactivation domain it can act as an antagonist of the MYC/MAX heterodimers. Variants of MAX have been reported to be linked to cancer. These variants are either not expressed, inactivated or lead to missense mutations. This has led to the notion that MAX may have a tumor suppressor role. Here, we characterize three of those variants with missense mutations in the basic region, i.e. E32K, R35P and R35C. We analyzed their heterodimerization with the b-HLH-LZ of MYC and their DNA binding properties as homo-and heterodimers. The R35C variant b-HLH-LZ was found to have a markedly increased affinity for the b-HLH-LZ of MYC. We also observed that all three b-HLH-LZ variants have a lower affinity as homodimers for the E-Box than the WT. This was shown to lead to a preferential binding of all the heterodimeric b-LHLH-LZ to the E-Box. This effect is exacerbated in the case of the R35C variant. We argue that this preferential binding of MYC as heterodimers with these variants to E-Box sequences could contribute to tumorigenesis. Hence, our results suggest that, mechanistically, the MAX homodimer bound to the E-Box could act as a tumor suppressor. MATERIALS AND METHODSO_ST_ABSMolecular modelingC_ST_ABSThe open source version 1.7.6.0 of Pymol was used for modeling and molecular rendering [1]. The crystal structure of the MAX homodimer bound to the E-Box (1HLO [2]) was used as a template for the generation of the models. The variants were generated using the mutagenesis function in the wizard. The conformation of the K32 side chain was manually set in order to avoid introducing steric clashes with DNA. Protein expression and purificationThe cDNA, coding for the MAX b-HLH-LZ (Max* hereafter, residues 22-103, UniProt entry P61244-1) to which are added the GSGC residues in c-terminal, inserted in the pET3a vector was already available in the laboratory [3] and was used as a template to generate the plasmids with inserts coding for each of the mutants (E32K, R35C and R35P) through quick-change PCR with Q5 DNA polymerase and DpnI from New England Biolabs. The primers used were purchased from IDT DNA, their sequences are listed in Table S1. Sequence for each construct was confirmed by Sanger sequencing at the Plateforme de sequencage SANGER - Centre de recherche du CHU de Quebec - Universite Laval. The primary structure for the basic region of each construct is given in Fig. 2A. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/715400v1_fig2.gif" ALT="Figure 2"> View larger version (41K): org.highwire.dtl.DTLVardef@1b05d5eorg.highwire.dtl.DTLVardef@1c1d692org.highwire.dtl.DTLVardef@ee469dorg.highwire.dtl.DTLVardef@15e0ba4_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOFigure 2.C_FLOATNO Structure schematics, specific and non-specific interactions dictating specificity and stability of binding of the basic region of MAX to the canonical (CACGTG) E-Box. A. Primary structure for the basic region of MAX and each of the variants. Positions making the most important contacts with the E-box are indicated by black arrows. Positions for the variants studied here are colored according to the Zappo colour scheme, following their physico-chemical properties: red for negative, blue for positive, magenta for proline and yellow for cysteine. B. The side chain (carboxylate) of E32 receives H-Bonds from the CA nucleobases in the leading strand (white carbon atoms). R35 and R36 make a salt bridges with phosphate groups while and the guanidino moiety of R36 makes a specific H-Bond with the nucleobase of the G in the strand of the reverse complement (cyan carbon atoms). C. The R35C mutation removes one non-specific salt-bridge at the interface of the complex. D. The aliphatic portion of the K side chain in the E32K variant is unable to accept the H-Bonds from the CA nucleobases and leads to the stabilisation of the complex and the helical structure of the basic region. E. In addition to removing a salt-bride, the Pro residue in the R35P kinks the path of the basic region, prevents the establishment of the specific H-Bonds mandatory for recognition of the E-Box and leads to unfolding of the helical state. C_FIG The MYC b-HLH-LZ (Myc*), the Max*WT b-HLH-LZ and its variants were expressed and purified as previously described [3,4] After lyophilisation, the b-HLH-LZs were kept at -20{degrees}C and solubilised in Myc buffer (50 mM NaCl, 50 mM NaH2PO4 pH 5.5) for Myc* or PBS for Max* at a final concentration of 1 mM before use. Circular dichroismAll circular dichroism (CD) measurements were performed on a Jasco J-810 spectropolarimeter equipped with a Peltier-type thermostat. The instrument was routinely calibrated using an aqueous solution of d-10-(+)-camphorsulfonic acid at 290.5 nm. Samples were prepared as follows: Max* (either WT or a variant) was diluted in 100 {micro}l 2X CD buffer (40 mM KCl, 11.4 mM K2HPO4, 28.6 mM KH2PO4, pH 6.8) and the volume adjusted to 106 {micro}l with PBS. 10 {micro}l TCEP 16 mM were added, and the volume further adjusted to 192 {micro}l with ddH2O before samples were incubated overnight at room temperature. After reduction, Myc* was added and the volume adjusted to 198 {micro}l with Myc buffer (Na2HPO4 0.95 mM, NaH2PO4 49.05 mM, 50 mM NaCl, pH 5.5). The DNA complexes were prepared as follows. After a 10 minutes incubation of the protein samples at room temperature, 0, 1 or 2 {micro}l of 2 mM of specific or non-specific DNA duplexes in 10 mM Tris pH 8.0 were added and the volume adjusted to 200 {micro}l with 10 mM Tris pH 8.0. The strands of the specific probe were: 5-ATT ACC CAC GTG TCC T*AC-3 and 5-GTA GGA CAC GTG GGT* AAT-3 (with the E-box sequence underlined) and the non-specific probe: 5-ATT ACC TCC GGA TCC T*AC-3 and 5-GTA GGA TCC GGA GGT* AAT-3 (Integrated DNA Technologies). Samples were further incubated for 10 minutes at room temperature and transferred to a 1 mm path length quartz cuvette. All spectra were recorded from 250 to 195 nm at 0.1 nm intervals by accumulating 10 spectra at 25 {degrees}C. Thermal denaturations were recorded at 222 nm from 5 to 95 {degrees}C at a heating rate of 1 {degrees}C/min. CD signal for spectra and thermal denaturations was corrected by substracting the signal from corresponding spectra or thermal denaturation either for buffer alone or the appropriate DNA duplex. CD signal was then converted to mean residue ellipticity using the following formula [5]: [{theta}] = {delta} {middle dot} MRW/(10{middle dot}c l) where [{theta}] is the mean residue ellipticity in deg {middle dot} cm2 dmol-1, {delta} is the CD signal in millidegrees, MRW is the mean residue weight, c is the concentration in mg/ml and l is the pathlength in mm. For the heterodimers, the concentration used was the sum of Max* and Myc* and the MRW was determined using a weighted average.

Transcriptomic analyses are widely used to elucidate the molecular mechanisms driving gametogenesis and reproduction in fish, yet their accuracy depends heavily on appropriate normalization of gene expression data. Conventional approaches that rely on single or multiple reference genes are problematic during teleost oogenesis, as profound structural and physiological remodeling of the ovary challenges the assumption that commonly used reference transcripts remain stable. In this study, we assessed by qPCR the transcriptional variability of four widely used reference genes (actb, ef-1, gapdh, and 18S rRNA) throughout the oogenic cycle of the thicklip grey mullet (Chelon labrosus), using geNorm and NormFinder analyses, and we additionally evaluated total cDNA concentration as an alternative normalization factor. To examine the performance and interpretive consequences of each normalization strategy, we compared expression patterns of key steroidogenic genes (star, cyp19a1a, and cyp11b) normalized by individual reference genes, combinations of reference genes, or total cDNA concentration. All evaluated reference genes displayed notable transcriptional variability across oogenesis, confirming their limited suitability as sole internal controls. In contrast, normalization approaches integrating multiple reference genes and/or total cDNA concentration consistently provided greater stability and more reliable biological interpretation. These results support a refined and more robust normalization framework for transcriptional analyses in fish ovaries, particularly during stages of extensive tissue remodeling. Our findings demonstrate cDNA-based normalization is straightforward, rapid, and easy to implement across laboratories, providing a practical alternative for achieving accurate, reproducible transcript quantification in fish ovary studies.

MicroRNAs (miRNAs) play essential roles in the posttranscriptional regulation of gene expression in organisms. In the process of synthesizing mature miRNAs from miRNA precursors, the miRNA precursors are cleaved via Dicer at their loop structure, after which the miRNA precursors become mature and regulate transcription. However, the consequences of altering the loop sequence are not fully understood. The silkworm Bombyx mori is a lepidopteran insect with many genetic strains. We identified a mutant of the miRNA miR-3260 whose the part of the loop structure was lacking in a silkworm strain with translucent larval skin. Here, we aimed to analyze the role of wild-type miR-3260 and the influence of the mutation of the loop structure in B. mori. First, we identified the genomic region responsible for the translucent larval skin phenotype and determined that the mutated miR-3260 nucleotide sequences. Then, we predicted the binding partners of wild-type miR-3260 using the RNA hybrid tool and found two juvenile hormone (JH)-related genes as targets of wild-type miR-3260. Next, we assessed the relationships between miR-3260 and JH and found that miR-3260 was highly expressed in the Corpora allata and its expression responded to JH treatment. Meanwhile, miR-3260 mimic and inhibitor did not induce the typical phenotypes associated with JH in B. mori. Then, we compared the dicing products from wild-type and mutant miR-3260 precursors and observed that neither form underwent Dicer-mediated cleavage when the loop structure was altered. These results suggest that loop mutations in the miR-3260 precursor may not influence dicing activity, consistent with the lack of observable phenotypic effects.

BackgroundThe most prevalent kind of oral cancer is oral squamous cell carcinoma (OSCC), which has a poor prognosis because of delayed detection and a lack of molecular indicators. MethodsTranscriptomic data from TCGA were analyzed to identify differentially expressed genes between OSCC and normal samples. Functional enrichment analysis was performed to determine biological pathways. A protein-protein interaction network was constructed using STRING and visualized in Cytoscape to identify hub genes. ResultsA total of 5732 differentially expressed genes were identified, including 2459 upregulated and 3273 downregulated genes. Network analysis revealed several highly connected hub genes such as CDK1, CCNB1, TOP2A, BUB1, and MMP9. Functional enrichment indicated significant involvement of cell cycle regulation and cancer-associated pathways. ConclusionThis integrative analysis identified key regulatory hub genes that may be involved in OSCC progression. These genes may serve as promising biomarkers and therapeutic targets for future studies.

Malaria is one of the deadliest diseases in sub-Saharan Africa and Southeast Asia. The majority of the fatalities occur mostly in children under 5 years and pregnant women and this is due to infection by Plasmodium spp, of which Plasmodium falciparum is the most virulent and is responsible for most of the morbidity and mortality. Despite various public health interventions such as use of insecticide-treated bed nets, spraying of homes with insecticides and use of WHO recommended artemisinin-based combination therapies (ACT), malaria prevention still faces major setback due to drug and insecticide resistance by P. falciparum and mosquitoes respectively. The study uses molecular docking and immunoinformatics to screen various Plasmodium spp antigens and evaluate their antigenicity and suitability as vaccine candidates. The P. falciparum antigens and T-cell receptor (TCR) structures were obtained from Protein Data Bank (PDB) based on a range of factors related to their role in the lifecycle of the parasite and their status as vaccine targets. Protein structures not available in the PDB were predicted using AlphaFold. The 3D structures of selected P. falciparum antigens and TCR structures were downloaded in PDB format then all water molecules, Hetatm, and bound ligands were deleted from the protein structures using BIOVIA Discovery Studio Visualizer. Subsequently, molecular docking was done using ClusPro v2.0 server and docked complexes were compared. The findings of this study gave valuable insights into the interaction of human immune response with P. falciparum antigens. The best three ranked antigen complexes are PfCyRPA, PfMSP10 and PfCSP and this confirm their use as potential candidates for vaccine development. This study highlights the usefulness of computational docking in identifying P. falciparum antigens of excellent immunogenic potential as vaccine candidates.

Background: Although thin, T1 melanomas have an excellent cure rate with surgery alone, >25% of melanoma deaths originate from thin melanomas (TMs). There is, therefore, an urgent need to improve the identification and management of patients with TMs at high risk of recurrence. Methods: Patients with T1 melanoma and recurrence [&le;] 2 years of diagnosis (T1 rapid group) were compared to patients with T1 melanoma and recurrence [&ge;]10 years after diagnosis (T1 late group). Results: 442 patients from 14 sites were included: 310 and 132 patients in the T1 rapid and late groups, respectively. Median age at primary melanoma diagnosis was 51 years [15-85], 272 (62%) male, 254 (58%) superficial spreading and 101 (23%) head/neck primary. The majority (73%) of recurrences in the T1 rapid group were locoregional. Using univariable logistic regression analysis, age >65 years (p<0.0001), lentigo maligna (LM) melanoma subtype (p=0.025), head/neck primary site (p=0.0065), mitoses [&ge;]1/mm2 (p=0.0181) and ulceration (p=0.0087) were significantly associated with T1 rapid recurrence compared to T1 late recurrence. Using multivariable analysis, age >65 years (p=0.0010), mitoses [&ge;]1/mm2 (p=0.049) and ulceration (p=0.037) remained significant. Conclusions: Rapid recurrence of TM is associated with age >65 years, LM subtype, head/neck primary site, mitoses [&ge;]1/mm2 and ulceration.

Abstract/SummaryO_ST_ABSBackgroundC_ST_ABSWhile numerous studies have explored the relationship between COVID-19 and cancer, few have specifically examined the significant impact of the pandemic on cancer patients, particularly concerning their treatments and appointments. ObjectivesThis study aims to investigate cancer treatment behaviors during the COVID-19 pandemic. MethodsThis retrospective quantitative study utilized data from the Centers for Disease Control and Preventions National Health Interview Survey of 2020. The inclusion criteria were as follows: studies conducted within the United States; patients diagnosed with COVID-19 since the pandemic began; patients diagnosed with cancer within the United States; patients undergoing cancer treatment or in remission since the start of the pandemic; patients who experienced a change, delay, or cancellation of treatment due to the COVID-19 pandemic; patients who experienced a change or delay in cancer care due to the COVID-19 pandemic; patients with a weakened immune system due to prescriptions; and patients who took prescription medication within the past 12 months. The variables were analyzed against population characteristics, including age, race, gender, cancer type, and COVID-19 status. Python Jupyter Notebook (packaged by Anaconda Navigator in R Studio, version 6.4.8), Microsoft Excel for data cleaning and assessment, and SPSS were used for statistical analyses. ResultsChi-Square Analysis (p<.05) revealed significant associations between cancer treatment and gender (p=0.009), other cancer treatments and age (p<.001) and education (p<.001), changes in other cancer treatments and gender (p=0.045), race (p<.001), age (p<.001), and education (p=.013), and prescribed medication and gender (p=.009), family income (p<.001), and age (p<.001). ConclusionThe COVID-19 pandemic has significantly impacted cancer care in the U.S., affecting the delivery of treatments. Additional government funding is necessary to help medical facilities develop programs for off-site treatment delivery, to better prepare for future pandemics, and avoid repeating past challenges.

ObjectiveTo quantify the gap between pregnancy desire and pregnancy attempts among young women with and without a history of breast cancer (BC), and to identify factors associated with this gap. DesignCross-sectional cohort study. SettingThe FEERIC study, conducted in France. PopulationWomen aged 18-43 years without or with prior BC filling inclusion forms of a collaborative study. MethodsPregnancy desire was assessed by self-report ("Do you currently desire a pregnancy?"). Attempt was defined as engaging in unprotected intercourse with the intention to conceive. The pregnancy desire-attempt gap was defined as expressing a desire for pregnancy without actively trying to conceive. Logistic regression was used to evaluate associated demographic, clinical, and treatment-related factors. Main outcome measuresPrevalence of the pregnancy desire-attempt gap and predictors of this gap among BC survivors. ResultsOf 4,351 participants (517 with BC and 3,834 controls), 735 (16.9%) reported a pregnancy desire with 54% attempting conception and 46% who did not. The desire-attempt gap was significantly more frequent in women with a history of BC (OR=1.62, 95%CI[1.15-2.30]). Among BC survivors, younger age (<30years), nulliparity, being single, and ongoing endocrine therapy were independently associated with the gap, whereas prior chemotherapy or trastuzumab were not. ConclusionsNearly half of women declaring desiring pregnancy do not initiate pregnancy attempts, with a larger gap among BC survivors. These findings highlight the need to explore both medical barriers and psychosocial determinants underlying this gap and underscore the importance of refining the language used in reproductive research. FundingThis study was supported by "SHS INCa" grant no.2016-124 and is part of a research project on young women funded by Monoprix*.

Colonic adenocarcinoma (COAD) is a major cause of cancer-related mortality worldwide. Various tumors are linked to metastasis-associated in colon cancer 1 (MACC1). This study aimed to analyze public datasets to examine MACC1 expression, signaling pathways, copy number variations, and associations with immune cell subsets in COAD employing bioinformatics. MACC1 expression was elevated in COAD, especially in Wnt signaling and chromatin modifier pathways. Analysis of somatic copy number alterations in The Cancer Genome Atlas-COAD dataset revealed a link between MACC1 and DNA damage repair. MACC1 also showed a negative correlation with genes involved in immune cell infiltration in patients with COAD, including cluster of differentiation (CD)8+ T cells, activated dendritic cells, CD8 T cells, and cytotoxic cells. Collectively, these findings suggest MACC1 as a potential prognostic biomarker and therapeutic target for COAD.

The early evolutionary history of modern domestic horses (Equus caballus/E. ferus caballus), known as the DOM2 lineage, is well documented due to numerous archaeological and ancient DNA (aDNA) studies. Although many uncertainties remain in the domestication timeline, current evidence suggests that the domestication of modern horses began in the Pontic-Caspian steppe at least [~]2700 BCE (before common era), or even earlier. However, it is not known how long remnant wild horse populations survived or when domestic horses were introduced into Northern Europe. In this study, we review the current knowledge of horse domestication, focusing on Northern Europe. We analysed prehistoric horses from western Russia to assess the body sizes of wild horses from the Ivanovskaya site (5900-3800 BCE) in the Pontic-Caspian steppe, and the body weight of one Lithuanian wild horse (4000-3800 BCE). Additionally, we analysed body sizes of Late Bronze Age-Early Roman Age horses (1100 BCE-300 CE; common era) and re-analysed body sizes and estimated rider weights of historic domestic horses from Lithuania (100-1400 CE). We searched for pathological changes and signs of bit wear indicative of bridling. Furthermore, we investigated maternal genetic diversity by sequencing ancient mitochondrial DNA. We found that wild horses from Ivanovskaya were intermediate in body size between earlier and more recent horses of the Eurasian Steppe, and that the Lithuanian wild horse weighed only [~]270 kg and Late Bronze Age-Early Roman Age horses 200-300 kg. Lithuanian domestic horses were pony-sized (< 130 cm on average). Bit wear was confirmed on one tooth, the oldest domestic horse in Lithuania (799-570 cal BCE). Another tooth showed signs of the Equine Odontoclastic Tooth Resorption and Hypercementosis (EOTRH) condition. Mitochondrial DNA was successfully amplified from one Ivanovskaya wild horse along with 25 other ancient samples, including Lithuanias oldest domestic horse. mtDNA diversity was high, revealing several maternal lineages.

The association between higher levels of physical activity and lower cancer risk and mortality is well established. However, a causal link is yet to be proven. Recent studies showed a decrease in the proliferation rates of cultured human cancer cells when the human serum employed to stimulate them was conditioned by acute exercise. Here, we tested the hypothesis that serum mediates some of the putative benefits of exercise on cancer through alterations to the growth pattern and susceptibility to chemotherapy agents of cancer cells. To this end, human non-small cell lung cancer (NSCLC) cells were exposed to serum from two cohorts that differed significantly on their levels of physical activity and, accordingly, cardiorespiratory fitness, but were otherwise identical (master athletes and non-exercisers), collected before and after an acute exercise intervention. Serum levels of glucose, lipids, albumin, C-reactive protein and cytokines were determined and the impact of the serum responses to acute and lifelong exercise on the above-mentioned parameters were analyzed. We found that acute exercise decreased the cells proliferation rate, yet shortened the cells lag phase after detachment, whereas lifelong exercise had the opposite effects. Significantly, we showed, for the first time, that lifelong exercise increased susceptibility to a chemotherapy agent (cisplatin), which may contribute to the decreased cancer mortality rates found among those who exercise regularly. Similar to the cellular effects, changes to serum cytokine levels - several of them linked to the senescence-associated secretory phenotype - depended on whether serum was conditioned by acute or by chronic exercise. Key pointsChronic exercise increased the in vitro susceptibility of lung cancer cells to cisplatin. Acute and chronic exercise modulated the in vitro tumorigenic potential of lung cancer cells. Effects were mediated by serological changes produced by exercise. Acute and chronic exercise had distinct impacts on serological cytokine levels.

Purpose Diabetic retinopathy (DR) is one of the most important complications of diabetes mellitus (DM), representing the leading cause of blindness among working age adults in developed countries. This study was aimed to investigate the epidemiology and risk factors of DR in patients with diabetes mellitus in a hospital setting in Somalia. Methods The study was an observational, descriptive cross-sectional and hospital-based study and data were collected from January 2023 to May 2023. A structured questionnaire was used to collect relevant demographic and clinical data. Both univariate and bivariate tables were used for analysis. Data analysis included frequency distribution, cross-tabulation, co-relation and association, and statistically significant tests between variables (X2, p-value, and CI). Results A total of 384 DM patients were studied and 76% (n=293) of them had type 2 DM. The average duration of diabetes mellitus was 9.7 SD 6.9 years and the mean age was 47.24 SD 19.36 years (range 18 -100 years old). A majority 66% (n=253) were female, about a third of them had normal body mass index (BMI) (n=172, 44.8%) and 170 (44.3%) had concomitant hypertension. About 51% of the patients (n=197) had DR out of which 17% had non-proliferative diabetic retinopathy (NPDR) (n=67) and 26% had Macular oedema (n=98). Age above 40 years (p=0.020), marital status (P=0.010), employment status (P=0.002) and literacy status (P=0.020) were significantly associated with the presence of DR. Patients aged below 40 had 37% lesser risk of having diabetic retinopathy than patients aged above 40 years. Longer duration of diabetes (p=0.001) and the presence of concomitant cardiac illness (p=0.001) were strongly associated with the presence of diabetic retinopathy. Patients with duration of diabetes more than 10 years had approximately 2 times higher chance of developing DR than those with duration less than 10 years. Conclusion: The very high prevalence of DR (51%) among our patients implies the needs for a good health policy to manage DM and DR patients in Somalia. Effective regular eye screening and treatment for all diabetes patients should get priority.