bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptome profiling of the initial segment and proximal caput of mouse epididymis
Authors: Wang Xiao , Qiu Fanyi , Yu Junjie , Zhou Meiyang , Zuo Anjian , Xu Xiaojiang , Sun Xiao-Yang , Wang Zhengpin 
Published: May 2023

BackgroundThe proximal region of the mouse epididymis plays a pivotal role in sperm transport, sperm maturation, and male fertility. Several studies have focused on segment-dependent gene expression of the mouse epididymis through high-throughput sequencing without the precision of the microdissection.Methods and resultsHerein, we isolated the initial segment (IS) and proximal caput (P-caput) by physical microdissection using anLcn9-cre;Rosa26tdTomatomouse model. We defined the transcriptome changes of caput epididymis by RNA sequencing (RNA-seq), which identified 1,961 genes that were abundantly expressed in the IS and 1,739 genes that were prominently expressed in the P-caput. In addition, we found that many differentially expressed genes (DEGs) were predominantly or uniquely expressed in the epididymis and region-specific genes were highly associated with transport, secretion, sperm motility, fertilization, and male fertility.ConclusionThus, this study provides an RNA-seq resource to identify region-specific genes in the caput epididymis. The epididymal-selective/specific genes are potential targets for male contraception and may provide new insights into understanding segment-specific epididymal microenvironment-mediated sperm transport, maturation, and male fertility.
Assessment of human milk samples obtained pre and post-influenza vaccination reveals a poor boosting of seasonally-relevant, hemagglutinin-specific antibodies
Authors: Yang Xiaoqi , DeCarlo Claire , Fox Alisa , Pineda Nicole , Powell Rebecca L. R. 
Published: May 2023

IntroductionInfluenza (flu) vaccination prevented over 100,000 hospitalizations and 7000 deaths from flu over the 2019-2020 season in the USA. Infants &lt;6 months are the most likely to die from flu, though flu vaccines are only licensed for infants &gt;6 months old. Therefore, it is recommended that flu vaccination occur during pregnancy, as this reduces severe complications; however, vaccination rates are suboptimal, and vaccination is also recommended postpartum. For breast/chest-fed infants, the vaccine is believed to elicit protective and robust seasonally-specific milk antibody (Ab). Few comprehensive studies exist examining Ab responses in milk after vaccination, with none measuring secretory Ab (sAb). Determining whether sAbs are elicited is critical, as this Ab class is highly stable in milk and mucosae.MethodsIn the present study, our aim was to determine to what extent specific Ab titers in the milk of lactating people were boosted after seasonal influenza vaccination. Over the 2019-2020 and 2020-2021 seasons, milk was obtained pre- and post-vaccination and assessed for specific IgA, IgG, and sAb against relevant hemagglutinin (HA) antigens by a Luminex immunoassay.ResultsIgA and sAb were not found to be significantly boosted, while only IgG titers against B/Phuket/3073/2013, included in vaccines since 2015, exhibited an increase. Across the 7 immunogens examined, as many as 54% of samples exhibited no sAb boost. No significant differences for IgA, sAb, or IgG boosting were measured between seasonally-matched versus mismatched milk groups, indicating boosting was not seasonally-specific. No correlations between IgA and sAb increases were found for 6/8 HA antigens. No boost in IgG- or IgA-mediated neutralization post vaccination was observed.DiscussionThis study highlights the critical need to redesign influenza vaccines with the lactating population in mind, wherein the aim should be to elicit a potent seasonally-specific sAb response in milk. As such, this population must be included in clinical studies.
Leveraging a disulfidptosis-based signature to improve the survival and drug sensitivity of bladder cancer patients
Authors: Chen Hualin , Yang Wenjie , Li Yingjie , Ma Lin , Ji Zhigang 
Published: May 2023

BackgroundDisulfidptosis is a recently discovered form of cell death. However, its biological mechanisms in bladder cancer (BCa) are yet to be understood.MethodsDisulfidptosis-related clusters were identified by consensus clustering. A disulfidptosis-related gene (DRG) prognostic model was established and verified in various datasets. A series of experiments including qRT-PCR, immunoblotting, IHC, CCK-8, EdU, wound-healing, transwell, dual-luciferase reporter, and ChIP assays were used to study the biological functions.ResultsWe identified two DRG clusters, which exhibited distinct clinicopathological features, prognosis, and tumor immune microenvironment (TIME) landscapes. A DRG prognostic model with ten features (DCBLD2, JAM3, CSPG4, SCEL, GOLGA8A, CNTN1, APLP1, PTPRR, POU5F1, CTSE) was established and verified in several external datasets in terms of prognosis and immunotherapy response prediction. BCa patients with high DRG scores may be characterized by declined survival, inflamed TIME, and elevated tumor mutation burden. Besides, the correlation between DRG score and immune checkpoint genes and chemoradiotherapy-related genes indicated the implication of the model in personalized therapy. Furthermore, random survival forest analysis was performed to select the top important features within the model: POU5F1 and CTSE. qRT-PCR, immunoblotting, and immunohistochemistry assays showed the enhanced expression of CTSE in BCa tumor tissues. A series of phenotypic assays revealed the oncogenetic roles of CTSE in BCa cells. Mechanically, POU5F1 can transactivate CTSE, promoting BCa cell proliferation and metastasis.ConclusionsOur study highlighted the disulfidptosis in the regulation of tumor progression, sensitivity to therapy, and survival of BCa patients. POU5F1 and CTSE may be potential therapeutic targets for the clinical treatment of BCa.
Visual evoked potentials waveform analysis to measure intracortical damage in a preclinical model of multiple sclerosis
Authors: Marenna Silvia , Rossi Elena , Huang Su-Chun , Castoldi Valerio , Comi Giancarlo , Leocani Letizia 
Published: May 2023

IntroductionVisual evoked potentials (VEPs) are a non-invasive technique routinely used in clinical and preclinical practice. Discussion about inclusion of VEPs in McDonald criteria, used for Multiple Sclerosis (MS) diagnosis, increased the importance of VEP in MS preclinical models. While the interpretation of the N1 peak is recognized, less is known about the first and second positive VEP peaks, P1 and P2, and the implicit time of the different segments. Our hypothesis is that P2 latency delay describes intracortical neurophysiological dysfunction from the visual cortex to the other cortical areas.MethodsIn this work, we analyzed VEP traces that were included in our two recently published papers on Experimental Autoimmune Encephalomyelitis (EAE) mouse model. Compared with these previous publications other VEP peaks, P1 and P2, and the implicit time of components P1-N1, N1-P2 and P1-P2, were analyzed in blind.ResultsLatencies of P2, P1-P2, P1-N1 and N1-P2 were increased in all EAE mice, including group without N1 latency change delay at early time points. In particular, at 7 dpi the P2 latency delay change was significantly higher compared with N1 latency change delay. Moreover, new analysis of these VEP components under the influence of neurostimulation revealed a decrease in P2 delay in stimulated animals.DiscussionP2 latency delay, P1-P2, P1-N1, and N1-P2 latency changes which reflect intracortical dysfunction, were consistently detected across all EAE groups before N1 change. Results underline the importance of analyzing all VEP components for a complete overview of the neurophysiological visual pathway dysfunction and treatment efficacy.
Sleep structure and related clinical characteristics in drug-naïve Parkinson's disease with subjectively different sleep quality
Authors: Jiang Yinyin , Chen Yaning , Li Dongfeng , Zhu Sha , Gu Ruxin , Wang Yaxi , Zhu Jun , Jiang Xu , Shen Bo , Pan Yang , Yan Jun , Zhang Li 
Published: May 2023

BackgroundSleep disturbance is a common non-motor symptom of Parkinson's disease (PD). Most polysomnography (PSG) studies are conducted when patients are in their “on medication” state. Our study aimed to investigate changes in the sleep structure in drug-naive PD patients with poor subjective sleep quality based on polysomnography (PSG) and to explore potential correlations between sleep structure and clinical features of the disease.MethodsA total of 44 drug-naive PD patients were included. All patients completed a standardized questionnaire to obtain demographic and clinical characteristics and underwent whole-night PSG recording. Patients with PSQI scores &gt;5.5 were considered poor sleepers, and patients with PSQI scores &lt;5.5 were considered to be good sleepers.ResultsThere were 24 (54.5%) PD patients in the good sleeper group and 20 (24.5%) PD patients in the poor sleeper group. We observed that poor sleepers had severe non-motor symptoms (NMS) and worse life quality. The PSG displayed that they had a longer wake-up time after sleep onset (WASO) and lower sleep efficiency (SE). Correlation analysis revealed that the micro-arousal index was positively associated with UPDRS-III, and the N1 sleep percentage was negatively associated with the NMS score in good sleepers. For poor sleepers, rapid eye movement (REM) sleep percentage was negatively related to the Hoehn-Yahr (H-Y) stage, WASO increased with UPDRS-III, periodic limb movement index (PLMI) increased with the NMS score, and N2 sleep percentage was negatively related to the score of life quality.ConclusionNight awakening is the main manifestation of decreased sleep quality in drug-naive PD patients. Poor sleepers have severe non-motor symptoms and poor life quality. Additionally, the increase in nocturnal arousal events may predict the progression of motor dysfunction.
Sex differences in olfactory cortex neuronal loss in aging
Authors: Alotaibi Majed M. , De Marco Matteo , Venneri Annalena 
Published: May 2023

IntroductionAging plays a major role in neurodegenerative disorders such as Alzheimer’s disease, and impacts neuronal loss. Olfactory dysfunction can be an early alteration heralding the presence of a neurodegenerative disorder in aging. Studying alterations in olfaction-related brain regions might help detection of neurodegenerative diseases at an earlier stage as well as protect individuals from any danger caused by loss of sense of smell.ObjectiveTo assess the effect of age and sex on olfactory cortex volume in cognitively healthy participants.MethodNeurologically healthy participants were divided in three groups based on their age: young (20–35 years; n = 53), middle-aged (36–65 years; n = 66) and older (66–85 years; n = 95). T1-weighted MRI scans acquired at 1.5 T were processed using SPM12. Smoothed images were used to extract the volume of olfactory cortex regions.ResultsANCOVA analyses showed significant differences in volume between age groups in the olfactory cortex (p ≤ 0.0001). In women, neuronal loss started earlier than in men (in the 4th decade of life), while in men more substantial neuronal loss in olfactory cortex regions was detected only later in life.ConclusionData indicate that age-related reduction in the volume of the olfactory cortex starts earlier in women than in men. The findings suggest that volume changes in olfaction-related brain regions in the aging population deserve further attention as potential proxies of increased risk of neurodegenerative diseases.
Diagnostic accuracy of the latest-generation digital PET/CT scanner for detection of metastatic lymph nodes in head and neck cancer
Authors: Butt Frederick , Dominguez-Konicki Lillian , Tocci Noah , Paydarfar Joseph , Seltzer Marc , Pastel David 
Published: May 2023

PurposeThe aim of this retrospective analysis was to assess the diagnostic accuracy of the latest-generation digital positron emission tomography/computed tomography (PET/CT) scanner in the detection of cervical lymph node metastasis in patients undergoing staging work-up for head and neck cancer.Materials and methodsA total of 55 consecutive patients with head and neck cancer at our institution who had a PET/CT after installation of the latest-generation PET/CT (Siemens Biograph Vision) who subsequently underwent surgical neck dissection were included. The nodal station location and number of reported PET/CT-positive metastatic lymph nodes were compared to a gold standard of final surgical pathology after neck dissection.ResultsIn total, 188 neck levels and 1,373 lymph nodes were resected; 56 neck levels (118 nodes) in 31 (56%) patients contained nodal metastases on surgical pathology. On a nodal level-by-level analysis, the overall sensitivity for the detection of lymph node metastases on the latest-generation PET/CT scanner was 96.4% and the specificity was 86.4%. The sensitivity and specificity for the neck side analysis were 94.0% and 63.7%, and for the individual patient analysis were 100% and 71%, respectively.ConclusionsIn this single-institution study, latest-generation PET/CT had a high sensitivity and moderate to high specificity for detecting cervical node metastasis in head and neck cancer. Compared to data from older PET/CT scanners, the sensitivity of the latest-generation PET/CT was slightly higher, while the specificity was similar or slightly lower. Physicians involved in the management of head and neck cancer should be aware of possible changes in the overall diagnostic accuracy when changing to a latest-generation PET/CT scanner.
Immunotherapy-related adverse events in real-world patients with advanced non-small cell lung cancer on chemoimmunotherapy: a Spinnaker study sub-analysis
Authors: Anpalakhan Shobana , Huddar Prerana , Behrouzi Roya , Signori Alessio , Cave Judith , Comins Charles , Cortellini Alessio , Addeo Alfredo , Escriu Carles , McKenzie Hayley , Barone Gloria , Murray Lisa , Pinato David J. , Ottensmeier Christian , Campos Sara , Muthuramalingam Sethupathi , Chan Samuel , Gomes Fabio , Banna Giuseppe L. 
Published: May 2023

BackgroundThe Spinnaker study evaluated survival outcomes and prognostic factors in patients with advanced non-small-cell lung cancer receiving first-line chemoimmunotherapy in the real world. This sub-analysis assessed the immunotherapy-related adverse effects (irAEs) seen in this cohort, their impact on overall survival (OS) and progression-free survival (PFS), and related clinical factors.MethodsThe Spinnaker study was a retrospective multicentre observational cohort study of patients treated with first-line pembrolizumab plus platinum-based chemotherapy in six United Kingdom and one Swiss oncology centres. Data were collected on patient characteristics, survival outcomes, frequency and severity of irAEs, and peripheral immune-inflammatory blood markers, including the neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII).ResultsA total of 308 patients were included; 132 (43%) experienced any grade irAE, 100 (32%) Grade 1–2, and 49 (16%) Grade 3–4 irAEs. The median OS in patients with any grade irAES was significantly longer (17.5 months [95% CI, 13.4–21.6 months]) than those without (10.1 months [95% CI, 8.3–12.0 months]) (p&lt;0.001), either if Grade 1–2 (p=0.003) or Grade 3–4 irAEs (p=0.042). The median PFS in patients with any grade irAEs was significantly longer (10.1 months [95% CI, 9.0–11.2 months]) than those without (6.1 months [95% CI, 5.2–7.1 months]) (p&lt;0.001), either if Grade 1–2 (p=0.011) or Grade 3–4 irAEs (p=0.036). A higher rate of irAEs of any grade and specifically Grade 1–2 irAEs correlated with NLR &lt;4 (p=0.013 and p=0.018), SII &lt;1,440 (p=0.029 ad p=0.039), response to treatment (p=0.001 and p=0.034), a higher rate of treatment discontinuation (p&lt;0.00001 and p=0.041), and the NHS-Lung prognostic classes (p=0.002 and p=0.008).ConclusionsThese results confirm survival outcome benefits in patients with irAEs and suggest a higher likelihood of Grade 1–2 irAEs in patients with lower NLR or SII values or according to the NHS-Lung score.
Association between red blood cell transfusion and bronchopulmonary dysplasia: a systematic review and meta-analysis
Authors: Tang Li , Zhu Ting Ting , Zhao Jing 
Published: May 2023

BackgroundWe aimed to determine the association between red blood cell transfusions (RBCT) and bronchopulmonary dysplasia (BPD) in neonates.MethodsA systematic review and meta-analysis were conducted using data obtained from literature search of PubMed, Embase, and Web of Science from their inception till May 1, 2022. Two reviewers independently selected potentially relevant studies, and after data extraction, they assessed the methodological quality of the included studies using the Newcastle–Ottawa scale. Data were pooled using random-effects models in Review Manager 5.3. Subgroup-analysis was performed based on the number of transfusions and adjusted results.ResultsOf the 1,011 identified records, 21 total case-control, cross-sectional, and cohort studies were selected, which included a total of 6,567 healthy controls and 1,476 patients with BPD. The pooled unadjusted odds ratio ([OR], 4.01; 95% confidence interval [CI] 2.31–6.97) and adjusted OR (5.11; 95% CI 3.11–8.4) showed significant association between RBCT and BPD. A substantial heterogeneity was noted, which could be due to different variables controlled for in each study. The subgroup analysis showed that heterogeneity may be partially explained by the extent of transfusion.ConclusionThe association between BPD and RBCT remains unclear based on the current data due to the substantial heterogeneity among the results. Well-designed studies are still needed in the future.
Impact of CYP2D6 genotype on opioid use disorder deprescription: an observational prospective study in chronic pain with sex-differences
Authors: Muriel Javier , Barrachina Jordi , Del Barco Guillermo , Carvajal Cristian , Escorial Mónica , Margarit César , Ballester Pura , Peiró Ana María 
Published: May 2023

Introduction: Opioid deprescription is the process of supervised tapering and safe withdrawal when a potentially inappropriate use is detected. This represents a challenge in chronic non-cancer pain (CNCP) patients who may respond differently to the procedure. Our aim was to analyze the potential impact of CYP2D6 phenotypes and sex on the clinical and safety outcomes during an opioid use disorder (OUD) tapering process.Methods: A prospective observational study was conducted on CNCP ambulatory OUD patients (cases, n = 138) who underwent a 6-month opioid dose reduction and discontinuation. Pain intensity, relief and quality of life (Visual analogue scale, VAS 0–100 mm), global activity (GAF, 0–100 scores), morphine equivalent daily dose (MEDD), analgesic drugs adverse events (AEs) and opioid withdrawal syndrome (OWS, 0–96 scores) were recorded at basal and final visits. Sex differences and CYP2D6 phenotypes (poor (PM), extensive (EM) and ultrarapid (UM) metabolizers based on CYP2D6*1, *2, *3, *4, *5, *6, *10, *17, *41, 2D6*5, 2D6 × N, 2D6*4 × 2 gene variants) were analyzed.Results: Although CYP2D6-UM consumed three-times less basal MEDD [40 (20–123) mg/day, p = 0.04], they showed the highest number of AEs [7 (6–11), p = 0.02] and opioid withdrawal symptoms (46 ± 10 scores, p = 0.01) after deprescription. This was inversely correlated with their quality of life (r = −0.604, p &lt; 0.001). Sex-differences were evidenced with a tendency to a lower analgesic tolerability in females and lower quality of life in men.Discussion: These data support the potential benefits of CYP2D6-guided opioid deprescription, in patients with CNCP when OUD is detected. Further studies are required to understand a sex/gender interaction.
Effect of the metal ion-induced carbonylation modification of mitochondrial membrane channel protein VDAC on cell vitality, seedling growth and seed aging
Authors: Li Ying , Liu Chang , Qi Manyao , Ye Tiantian , Kang Ying , Wang Yu , Wang Xiaofeng , Xue Hua 
Published: May 2023

IntroductionSeeds are the most important carrier of germplasm preservation. However, an irreversible decrease in vigor can occur after the maturation of seeds, denoted as seed aging. Mitochondrion is a crucial organelle in initiation programmed cell death during seed aging. However, the underlying mechanism remains unclear.MethodsOur previous proteome study found that 13 mitochondria proteins underwent carbonylation modification during the aging of Ulmus pumila L. (Up) seeds. This study detected metal binding proteins through immobilized metal affinity chromatography (IMAC), indicating that metal binding proteins in mitochondria are the main targets of carbonization during seed aging. Biochemistry, molecular and cellular biology methods were adopted to detect metal-protein binding, protein modification and subcellular localization. Yeast and Arabidopsis were used to investigate the biological functions in vivo.Results and discussionIn IMAC assay, 12 proteins were identified as Fe2+/Cu2+/Zn2+ binding proteins, including mitochondrial voltage dependent anion channels (VDAC). UpVDAC showed binding abilities to all the three metal ions. His204Ala (H204A) and H219A mutated UpVDAC proteins lost their metal binding ability, and became insensitive to metal-catalyzed oxidation (MCO) induced carbonylation. The overexpression of wild-type UpVDAC made yeast cells more sensitive to oxidative stress, retarded the growth of Arabidopsis seedlings and accelerated the seed aging, while overexpression of mutated UpVDAC weakened these effects of VDAC. These results reveal the relationship between the metal binding ability and carbonylation modification, as well as the probable function of VDAC in regulating cell vitality, seedling growth and seed aging.
Anxiety, depression, and quality of life in postoperative non-small cell lung cancer patients under the intervention of cognitive-behavioral stress management
Authors: Wang Fengju , Zhang Shuyan , Song Bingbing , Han Yuxiang 
Published: May 2023

ObjectiveCognitive-behavioral stress management (CBSM) is a psychotherapy that helps patients cognize and manage stress to improve mental health and quality of life. This study aimed to explore the influence of CBSM on anxiety, depression, and quality of life in non-small cell lung cancer (NSCLC) patients.MethodsIn total, 172 NSCLC patients who received tumor resection were randomized 1:1 into the usual care (UC) group (N = 86) and CBSM group (N = 86) to receive 10-week UC and CBSM interventions. Moreover, all participants attended a 6-month follow-up.ResultsHospital Anxiety and Depression Scales (HADS)-anxiety score at 3rd month (M3) (P = 0.015) and 6th month (M6) (P = 0.018), HADS-depression score at M3 (P = 0.040) and M6 (P = 0.028), and depression rate at M6 (P = 0.035) were descended in CBSM group compared to UC group. Besides, depression severity was reduced at M6 (P = 0.041) in CBSM group compared to UC group, but anxiety severity only showed a decreased trend (P = 0.051). Additionally, Quality of Life Questionnaire-Core 30 (QLQ-C30) global health status score and QLQ-C30 function score at 1st month (M1), M3, and M6 were elevated (all P &lt; 0.05), while QLQ-C30 symptoms score was declined at M1 (P = 0.031) and M3 (P = 0.014) in CBSM group compared to UC group. Notably, the efficacy of CBSM was impressive in patients with baseline depression or undergoing adjuvant therapy.ConclusionCBSM is a feasible intervention that effectively improves mental health and quality of life in postoperative NSCLC patients.