bluuebunny/crossref_metadata_2025_split huggingface dataset:
Whole genome sequence analysis of apparent treatment resistant hypertension status in participants from the Trans-Omics for Precision Medicine program
Authors: Armstrong Nicole D. , Srinivasasainagendra Vinodh , Ammous Farah , Assimes Themistocles L. , Beitelshees Amber L. , Brody Jennifer , Cade Brian E. , Ida Chen Yii-Der , Chen Han , de Vries Paul S. , Floyd James S. , Franceschini Nora , Guo Xiuqing , Hellwege Jacklyn N. , House John S. , Hwu Chii-Min , Kardia Sharon L. R. , Lange Ethan M. , Lange Leslie A. , McDonough Caitrin W. , Montasser May E. , O’Connell Jeffrey R. , Shuey Megan M. , Sun Xiao , Tanner Rikki M. , Wang Zhe , Zhao Wei , Carson April P. , Edwards Todd L. , Kelly Tanika N. , Kenny Eimear E. , Kooperberg Charles , Loos Ruth J. F. , Morrison Alanna C. , Motsinger-Reif Alison , Psaty Bruce M. , Rao Dabeeru C. , Redline Susan , Rich Stephen S. , Rotter Jerome I. , Smith Jennifer A. , Smith Albert V. , Irvin Marguerite R. , Arnett Donna K. 
Published: December 2023

Introduction: Apparent treatment-resistant hypertension (aTRH) is characterized by the use of four or more antihypertensive (AHT) classes to achieve blood pressure (BP) control. In the current study, we conducted single-variant and gene-based analyses of aTRH among individuals from 12 Trans-Omics for Precision Medicine cohorts with whole-genome sequencing data.Methods: Cases were defined as individuals treated for hypertension (HTN) taking three different AHT classes, with average systolic BP ≥ 140 or diastolic BP ≥ 90 mmHg, or four or more medications regardless of BP (n = 1,705). A normotensive control group was defined as individuals with BP &lt; 140/90 mmHg (n = 22,079), not on AHT medication. A second control group comprised individuals who were treatment responsive on one AHT medication with BP &lt; 140/ 90 mmHg (n = 5,424). Logistic regression with kinship adjustment using the Scalable and Accurate Implementation of Generalized mixed models (SAIGE) was performed, adjusting for age, sex, and genetic ancestry. We assessed variants using SKAT-O in rare-variant analyses. Single-variant and gene-based tests were conducted in a pooled multi-ethnicity stratum, as well as self-reported ethnic/racial strata (European and African American).Results: One variant in the known HTN locus, KCNK3, was a top finding in the multi-ethnic analysis (p = 8.23E-07) for the normotensive control group [rs12476527, odds ratio (95% confidence interval) = 0.80 (0.74–0.88)]. This variant was replicated in the Vanderbilt University Medical Center’s DNA repository data. Aggregate gene-based signals included the genes AGTPBP, MYL4, PDCD4, BBS9, ERG, and IER3.Discussion: Additional work validating these loci in larger, more diverse populations, is warranted to determine whether these regions influence the pathobiology of aTRH.
First case report of a novel KIF13A-ALK fusion in a lung adenocarcinoma patient and response to alectinib with a 4-year follow-up
Authors: Mo Zheng , Cai Cunliang , Yao Jingjing , Zhao Jingquan , Zhang Mingqiang , Liu Hao , Mu Xiangdong 
Published: December 2023

The prevalence of Anaplastic Lymphoma Kinase gene (ALK) fusion is about 5% among patients with lung adenocarcinoma, underscoring the importance of pinpointing distinct fusion variants for optimizing treatment approaches. This is the first reported case of a 74-year-old female with stage IV lung adenocarcinoma, featuring a novel Kinesin Family Member 13A (KIF13A)-ALK fusion, identified via next-generation sequencing (NGS) and confirmed with fluorescence in situ hybridization (FISH). Initially undergoing chemotherapy and then crizotinib, she achieved a partial response (PR) before progressing with multiple bone metastases. However, subsequent treatment with alectinib as a third-line option yielded positive results. A stable disease state persisted for an impressive 31 months of progression-free survival (PFS), accompanied by minimal toxicity symptoms. Up until now, a remarkable near 4-year span of overall survival (OS) has been consistently observed and monitored. This report of a KIF13A-ALK fusion case benefit significantly from alectinib with extensive follow-up. The case diversifies the array of ALK fusion partners and holds clinical relevance in refining therapeutic choices for KIF13A-ALK fusion-associated lung cancer.
Divergent neuroimmune signatures in the cerebrospinal fluid predict differential gender-specific survival among patients with HIV-associated cryptococcal meningitis
Authors: Okurut Samuel , Boulware David R. , Okafor Elizabeth , Rhein Joshua , Kajumbula Henry , Bagaya Bernard S. , Bwanga Freddie , Olobo Joseph O. , Manabe Yukari C. , Meya David B. , Janoff Edward N. 
Published: December 2023

IntroductionSurvival among people with HIV-associated cryptococcal meningitis (CM) remains low, particularly among women, despite the currently optimal use of antifungal drugs. Cryptococcus dissemination into the central nervous system [brain, spinal cord, and cerebrospinal fluid (CSF)] elicits the local production of cytokines, chemokines, and other biomarkers. However, no consistent diagnostic or prognostic neuroimmune signature is reported to underpin the risk of death or to identify mechanisms to improve treatment and survival. We hypothesized that distinct neuroimmune signatures in the CSF would distinguish survivors from people who died on antifungal treatment and who may benefit from tailored therapy.MethodsWe considered baseline clinical features, CSF cryptococcal fungal burden, and CSF neuroimmune signatures with survival at 18 weeks among 419 consenting adults by “gender” (168 women and 251 men by biological sex defined at birth).ResultsSurvival at 18 weeks was significantly lower among women than among men {47% vs. 59%, respectively; hazard ratio (HR) = 1.4 [95% confidence interval (CI), 1.0 to 1.9; p = 0.023]}. Unsupervised principal component analysis (PCA) demonstrated divergent neuroimmune signatures by gender, survival, and intragender-specific survival. Overall, women had lower levels of programmed death ligand 1, Interleukin (IL) (IL-11RA/IL-1F30, and IL-15 (IL-15) than men (all p &lt; 0.028). Female survivors compared with those who died expressed significant elevations in levels of CCL11 and CXCL10 chemokines (both p = 0.001), as well as increased T helper 1, regulatory, and T helper 17 cytokines (all p &lt; 0.041). In contrast, male survivors expressed lower levels of IL-15 and IL-8 compared with men who died (p &lt; 0.044).ConclusionsSurvivors of both genders demonstrated a significant increase in the levels of immune regulatory IL-10. In conclusion, the lower survival among women with CM was accompanied by distinct differential gender-specific neuroimmune signatures. These female and male intragender-specific survival–associated neuroimmune signatures provide potential targets for interventions to advance therapy to improve the low survival among people with HIV-associated CM.
Unique characteristics of the tumor immune microenvironment in young patients with metastatic colorectal cancer
Authors: Griffith Brian D. , Lazarus Jenny , McGue Jake , Krishnan Santhoshi , D’Angelica Michael I. , Shia Jinru , Dobrosotskaya Irina , Shi Jaiqi , Edwards Jacob , Rao Arvind , Frankel Timothy L. 
Published: December 2023

IntroductionMetastatic colorectal cancer (mCRC) remains a common and highly morbid disease, with a recent increase in incidence in patients younger than 50 years. There is an acute need to better understand differences in tumor biology, molecular characteristics, and other age-related differences in the tumor microenvironment (TME).Methods111 patients undergoing curative-intent resection of colorectal liver metastases were stratified by age into those &lt;50 years or &gt;65 years old, and tumors were subjected to multiplex fluorescent immunohistochemistry (mfIHC) to characterize immune infiltration and cellular engagement.ResultsThere was no difference in infiltration or proportion of immune cells based upon age, but the younger cohort had a higher proportion of programmed death-ligand 1 (PD-L1)+ expressing antigen presenting cells (APCs) and demonstrated decreased intercellular distance and increased cellular engagement between tumor cells (TCs) and cytotoxic T lymphocytes (CTLs), and between TCs and APCs. These trends were independent of microsatellite instability in tumors.DiscussionAge-related differences in PD-L1 expression and cellular engagement in the tumor microenvironment of patients with mCRC, findings which were unrelated to microsatellite status, suggest a more active immune microenvironment in younger patients that may offer an opportunity for therapeutic intervention with immune based therapy.
The general public’s attitude towards accepting payment for kidney donation
Authors: Gonen Limor Dina , Bokek-Cohen Ya’arit , Tarabeih Mahdi 
Published: December 2023

IntroductionKidney transplantation has become the most cost-effective treatment for patients with end-stage kidney disease (ESKD) and offers them the highest quality of life. Yet, kidney donation is often inaccessible due to cultural and traditional beliefs about organ donation. The goal of our study is to assess the value of kidney donation using the Willingness to Accept (WTA) technique. We also aim to understand the factors influencing an individual’s willingness to donate an organ.MethodsA self-administered survey was completed by 985 participants from the general public. The quantitative method and survey design that were chosen used descriptive, correlational, nonparametric, and multivariate statistical tests.ResultsMost of the respondents, 895 (90.9%) are not willing to donate a kidney while alive. Four hundred and five (41.1%) of the respondents are not willing to donate a kidney after their death, while the rest are willing to donate their kidney after their death without financial compensation. The same attitude applies to the donation of a kidney from their relatives. Significant predictors from the results of the logistic regression model in predicting the lowest (minimal) amount that will encourage donation of one kidney after death were: Marital status; Nationality; Adi card holder; Knowing people who need a kidney donation; confidence in the medical staff; and consideration of the family’s opinions regarding organ donation.DiscussionUsing cost benefit analysis (CBA), with the aim of evaluating the willingness of individuals to accept payment for innovative medical procedures, such as kidney donation, allows an assessment of the perceived value of the medical procedure and enables policymakers to decide whether to allocate funds or offer subsidies for kidney donation, given the limited healthcare resources available. During our research, we found that most participants did not support the commercialization of organs. Our recommendation for policymakers and health professionals is to continue providing adequate funding for kidney donations and to implement educational programs aimed at improving attitudes towards organ donation.
Periodontitis relates to benign prostatic hyperplasia via the gut microbiota and fecal metabolome
Authors: Guo Xing-Pei , Yang Jun , Wu Lan , Fang Cheng , Gu Jia-Min , Li Fei , Liu Han-Song , Li Lu-Yao , Wang Shuang-Ying 
Published: December 2023

ObjectivesPeriodontitis is associated with benign prostatic hyperplasia (BPH), whether it related to gut floramicrobiota and metabonomics is unclear.MethodsWe established ligature-induced periodontitis (EP), testosterone-induced BPH, and composite rat models. Fecal samples were collected to detect gut microbiota by 16S rDNA sequencing and metabonomics were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS).ResultsSequencing results revealed differential gut floramicrobiota composition between EP+BPH group and other three groups. The abundances of Ruminococcus flavefaciens were significantly increased in EP+BPH group compared with other groups. Tenericutes, Mollicutes, RF39 and Ruminococcus gnavus were significantly decreased in EP+BPH group compared with BPH group, while Ruminococcus callidus and Escherichia were significantly decreased compared with EP group. For gut metabonomics, LC-MS/MS showed that fecal metabolites and seven metabolic pathways were changed in EP+BPH group, such as biosynthesis of unsaturated fatty acids, steroid hormone biosynthesis. Correlation analysis showed that the alterations of gut metabolism were significantly correlated with differential gut floramicrobiota, such as Ruminococcus callidus and Ruminococcus flavefaciens.ConclusionOur study highlights the relationship of periodontitis and BPH, the alterations of gut floramicrobiota and metabolites may be involved in two diseases, which provides new idea for prevention and treatment of patients with periodontitis concurrent BPH.
Identification of the human cerebral cortical hemodynamic response to passive whole-body movements using near-infrared spectroscopy
Authors: Zhao Yue , Wei Yue , Wang Yixuan , So Richard H. Y. , Chan Chetwyn C. H. , Cheung Raymond T. F. , Wilkins Arnold 
Published: December 2023

The human vestibular system is crucial for motion perception, balance control, and various higher cognitive functions. Exploring how the cerebral cortex responds to vestibular signals is not only valuable for a better understanding of how the vestibular system participates in cognitive and motor functions but also clinically significant in diagnosing central vestibular disorders. Near-infrared spectroscopy (NIRS) provides a portable and non-invasive brain imaging technology to monitor cortical hemodynamics under physical motion.ObjectiveThis study aimed to investigate the cerebral cortical response to naturalistic vestibular stimulation induced by real physical motion and to validate the vestibular cerebral cortex previously identified using alternative vestibular stimulation.ApproachFunctional NIRS data were collected from 12 right-handed subjects when they were sitting in a motion platform that generated three types of whole-body passive translational motion (circular, lateral, and fore-and-aft).Main resultsThe study found that different cortical regions were activated by the three types of motion. The cortical response was more widespread under circular motion in two dimensions compared to lateral and fore-and-aft motions in one dimensions. Overall, the identified regions were consistent with the cortical areas found to be activated in previous brain imaging studies.SignificanceThe results provide new evidence of brain selectivity to different types of motion and validate previous findings on the vestibular cerebral cortex.
Radioprotective potential of whey protein against gamma irradiation-induced lingual damage
Authors: Hassan Hanaa M. , Abdeen Asmaa M. , Abdelrahman Ibrahim Y. , Abdo Walied , Mohammed Saher S. , Abdeen Ahmed , Abdelkader Afaf , Olga Rada , Fericean Liana , Ibrahim Samah F. , Ghamry Heba I. , Elgendy Farouk S. , Sorour Safwa M. , Eldeeb Abeer A. , Ahmed Osama , Rashed Fatema , Bikheet Maha M. 
Published: December 2023

Introduction: Ionizing radiation (IR) is effectively used in the treatment of oral malignancies; however, it might also significantly harm the surrounding tissues. Whey protein isolate (WP) is a protein derived from milk that exhibits a wide range of bioactivities. Therefore, the present research aimed to delineate the mitigating impact of WP against gamma irradiation-induced lingual damage.Methods: Rats were randomized into 5 groups: Control (saline, orally, 14 days), WP (WP; 0.5 g/kg b. w., orally, 14 days), IR (saline, orally, 14 days, exposed to 6 and 3 Gy on days 4 and 6, respectively), WP+IR (WP was given orally for 14 days before and after IR exposure; exposed to 6 and 3 Gy on days 4 and 6, respectively), and IR+WP (WP, orally, started 24 h after 1st IR exposure till the end of the experiment) groups. Samples were collected at two-time intervals (on the 7th and 14th days).Results and Discussion: Oxidative stress was stimulated upon IR exposure in tongue, indicated by boosted malondialdehyde (MDA) level, along with a decrease in the total antioxidant capacity (TAC) level, superoxide dismutase (SOD), and catalase (CAT) activities. Additionally, IR exposure depicted an increase of serum IgE, inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, along with overexpression mRNA levels of nuclear factor kappa-B transcription factor/p65 (NF-κB/p65), and down-regulation of nuclear factor erythroid 2–related factor 2 (NRF2) and heme oxygenase (HO-1) mRNA levels in tongue tissue. Moreover, IR triggered alterations in lingual histological architecture. The antioxidant and anti-inflammatory properties of WP mitigated oxidative damage, inflammation, and desquamation that were brought on following IR exposure. The protective administration of WP markedly decreases IR-induced lingual harm compared to the mitigation protocol. Our findings recommend WP supplements to the diets of cancer patients undergoing IR that might aid radioprotective effects.
The efficacy of intranasal leptin for opioid-induced respiratory depression depends on sex and obesity state
Authors: Singer Michele L. , Shin Mi-Kyung , Kim Lenise J. , Freire Carla , Aung O , Pho Huy , East Joshua A. , Sgambati Frank P. , Latremoliere Alban , Pham Luu V. , Polotsky Vsevolod Y. 
Published: December 2023

Introduction: Opioid-induced respiratory depression (OIRD) is the primary cause of death associated with opioids and individuals with obesity are particularly susceptible due to comorbid obstructive sleep apnea (OSA). Repeated exposure to opioids, as in the case of pain management, results in diminished therapeutic effect and/or the need for higher doses to maintain the same effect. With limited means to address the negative impact of repeated exposure it is critical to develop drugs that prevent deaths induced by opioids without reducing beneficial analgesia.Methods: We hypothesized that OIRD as a result of chronic opioid use can be attenuated by administration of IN leptin while also maintaining analgesia in both lean mice and mice with diet-induced obesity (DIO) of both sexes. To test this hypothesis, an opioid tolerance protocol was developed and a model of OIRD in mice chronically receiving morphine and tolerant to morphine analgesia was established. Subsequently, breathing was recorded by barometric plethysmography in four experimental groups: obese male, obese female, lean male, and lean female following acute administration of IN leptin. Respiratory data were complemented with measures of arterial blood gas. Operant behavioral assays were used to determine the impact of IN leptin on the analgesic efficacy of morphine.Results: Acute administration of IN leptin significantly attenuated OIRD in DIO male mice decreasing the apnea index by 58.9% and apnea time by 60.1%. In lean mice leptin was ineffective. Blood gas measures confirmed the effectiveness of IN leptin for preventing respiratory acidosis in DIO male mice. However, IN leptin was not effective in lean mice of both sexes and appeared to exacerbate acid-base disturbances in DIO female mice. Additionally, morphine caused a complete loss of temperature aversion which was not reduced by intranasal leptin indicating IN leptin does not decrease morphine analgesia.Discussion: IN leptin effectively treated OIRD in morphine-tolerant DIO male mice without impacting analgesia. In contrast, IN leptin had no effect in lean mice of either sex or DIO female mice. The arterial blood gas data were consistent with ventilatory findings showing that IN leptin reversed morphine-induced respiratory acidosis only in DIO male mice but not in other mouse groups. Finally, a hypercapnic sensitivity study revealed that IN leptin rescued minute ventilation under hypercapnic conditions only in DIO male mice, which suggests that differential responses to IN leptin are attributable to different leptin sensitivities depending on sex and the obesity status.
The effectiveness of a rational-emotive intervention on teachers’ unconditional self-acceptance, perfectionism, and pupil control ideology
Authors: Samfira Elena Mirela , Sava Florin Alin 
Published: December 2023

IntroductionThe present research aimed to investigate the effectiveness of a Rational Emotive Behavior Therapy (REBT) intervention on in-service teachers.MethodsA quasi-experimental 2-group (intervention vs. control) × 3-time (pre, post-test, follow-up) design was applied to explore to what extent the REBT interventions help teachers increase their level of unconditional self-acceptance as the primary outcome and decrease their perfectionism tendencies and pupil control ideology as secondary outcomes. The sample consisted of 100 in-service teachers assigned to either the intervention group (n = 50) or the control group (n = 50). The experimental group received a 6-week intervention program. Every session was held weekly and lasted 90–120 min. The Unconditional Self-Acceptance Questionnaire (USAQ), Pupil Control Ideology Scale (PCI), and Perfectionism Inventory Scale (PI) were used to collect data. This study used a mixed model ANOVA 2 × 3 for data analysis.ResultsThe results indicated that in the experimental group, there was a statistically significant increase in unconditional self-acceptance level from pre-test to post-test, which remains significant at the 6-month follow-up. Likewise, there were no statistically significant differences in unconditional self-acceptance levels between the post-test and 6-month follow-up in the intervention group.DiscussionThese findings prove that REBT interventions are effective in increasing teachers’ unconditional self-acceptance.
Stanford neuromodulation therapy for treatment-resistant depression: a systematic review
Authors: Lan Xian-Jun , Cai Dong-Bin , Liu Qi-Man , Qin Zhen-Juan , Pridmore Saxby , Zheng Wei , Xiang Yu-Tao 
Published: December 2023

ObjectiveThis systematic review of randomized controlled studies (RCTs) and observational studies evaluated the efficacy and safety of stanford neuromodulation therapy (SNT) for patients with treatment-resistant depression (TRD).MethodsA systematic search (up to 25 September, 2023) of RCTs and single-arm prospective studies was conducted.ResultsOne RCT (n = 29) and three single-arm prospective studies (n = 34) met the study entry criteria. In the RCT, compared to sham, active SNT was significantly associated with higher rates of antidepressant response (71.4% versus 13.3%) and remission (57.1% versus 0%). Two out of the three single-arm prospective studies reported the percentage of antidepressant response after completing SNT, ranging from 83.3% (5/6) to 90.5% (19/21). In the three single-arm prospective studies, the antidepressant remission rates ranged from 66.7% (4/6) to 90.5% (19/21). No severe adverse events occurred in all the four studies.ConclusionThis systematic review found SNT significantly improved depressive symptoms in patients with TRD within 5 days, without severe adverse events.