bluuebunny/crossref_metadata_2025_split huggingface dataset:
Low Endogenous LH on the COS Initiation Day of a GnRH-Agonist Regimen Increases the Risk of Early Pregnancy Loss and Adverse ART Outcomes
Authors: Luo Xi , Li Lei , Lin Na , Ma Rui , Li Yonggang , Wu Ze 
Published: February 2022

ObjectiveTo assess the impact of serum luteinizing hormone (LH) levels on the day of initiation of controlled ovarian stimulation (COS) after pituitary suppression on early pregnancy loss and assisted reproductive technology (ART) outcomes.DesignRetrospective cohort study.SettingUniversity-affiliated hospital.PatientsA total of 9540 normogonadotrophic patients were treated with a GnRH agonist for in vitro fertilization (IVF). Based on the serum concentration of LH on the COS initiation day, patients were divided into low (&lt;1 mIU/mL, n=2838), medium (1–1.49 mIU/mL, n=3357), or high (≥1.5 mIU/mL, n=3345) LH groups and received either fresh embryo transfer (ET) or frozen ET (women with high ovarian response, insufficient endometrial thickness, or requesting frozen ET). A total of 6279 cycles were fresh ET (1960, 2222, and 2097 in the low, medium, and high LH groups, respectively).Intervention(s)During IVF/ICSI, a GnRH agonist was used to suppress pituitary function in the midluteal phase or follicular phase, and then gonadotropin was used to induce COS.Main Outcome Measure(s)The early pregnancy loss rate (ePLR) and live-birth rate (LBR) for fresh ET, as well as the cumulative ePLR and LBR for the entire ovarian stimulation cycle, were compared.ResultsIn the fresh ET cycles, the high, medium and low LH groups had an ePLR of 8.6%, 11.9% and 12.5%, respectively, and LBR of 42.1%, 37.9% and 37.5%, respectively. There were no significant differences in terms of clinical pregnancy rate (CPR), late pregnancy loss rate (lPLR), and ectopic pregnancy rate (EPR) among the three LH groups. For the entire ovarian stimulation cycle, the high LH group had a greater number of retrieved oocytes compared with the low and medium LH groups. Among the groups of high, medium and low LH, the cumulative CPR were 72.8%, 69.8% and 68.8%, respectively, and the cumulative LBR were 63.4%, 60.4% and 58.5%, respectively. There were no significant differences in the cumulative ePLR, lPLR, or EPR. After multivariable logistic regression, compared with the high LH group, the adjusted odds ratio of early pregnancy loss in the low and medium LH group were 1.429 (1.065-1.919, P = 0.018) and 1.389 (1.041-1.853, P = 0.026).ConclusionsAfter pituitary suppression by a GnRH-agonist during IVF, a low LH level (&lt;1.5 mIU/mL) on the COS initiation day was associated with adverse ART outcomes—including fewer oocytes, higher ePLR and lower LBR in fresh ET—and lower cumulative CPR and LBR in the entire ovarian-stimulation cycle. And LH on the COS initiation day was an independent factor affecting ePLR after multivariate regression.
Investigation of Heavy Metal Accumulation in Vegetables and Health Risk to Humans From Their Consumption
Authors: Gupta Neha , Yadav Krishna Kumar , Kumar Vinit , Prasad Shiv , Cabral-Pinto Marina M. S. , Jeon Byong-Hun , Kumar Sandeep , Abdellattif Magda H. , Alsukaibia Abdulmohsen Khalaf Dhahi 
Published: February 2022

Heavy metals contamination of soil and edible parts of vegetables is presently a challenging environmental issue worldwide. The present study determined the accumulated amount of cadmium (Cd), lead (Pb), nickel (Ni), cobalt (Co), zinc (Zn), copper (Cu), and manganese (Mn) in soil, coriander, onion, and tomato collected from agricultural fields of Jhansi city, India. The bio-concentration factor and non-carcinogenic health risks were also assessed to know the vegetables’ accumulation potential of heavy metals from soil and possibility to have non-carcinogenic health risks via an intake of these vegetables. The samples were digested using di-acid solution prior to heavy metals analysis by atomic absorption spectrometric method. The average content of Cd, Pb, Ni, Co, Zn, Cu, and Mn were 2.02, 19.09, 21.56, 9.31, 35.34, 14.96, and 15.21 mg/kg dry weight (dw) in soil, 0.23, 2.12, 0.77, 0.47, 36.65, 5.92, and 21.65 mg/kg dw in coriander, 0.13, 0.66, 0.54, 0.32, 23.94, 6.25, and 20.15 mg/kg dw in onion, 0.14, 0.46, 0.89, 0.22, 16.77, 4.77, and 14.46 mg/kg dw in tomato, respectively. The bio-concentration factor revealed significant accumulation of Zn (1.04) and Mn in coriander (1.42), and in onion (1.32). The target hazard quotient and health risk index signaled that the population consuming these vegetables is risk-free. However, it is recommended that the concentration of heavy metals in the soil and crops of the study area and its related health risks be regularly monitored to avoid significant health risks in the future.
TIGIT Signaling Pathway Regulates Natural Killer Cell Function in Chronic Hepatitis B Virus Infection
Authors: Wang Juan , Hou Hongyan , Mao Lie , Wang Feng , Yu Jing , Luo Ying , Lin Qun , Sun Ziyong 
Published: February 2022

Background and ObjectivePersistent infection of hepatitis B virus (HBV) and liver damage in immune active chronic hepatitis B (CHB) could be partly due to the overreaction of natural killer (NK) cells, including pro-inflammatory cytokine secretion and cytotoxicity. An immunosuppressive receptor, T-cell immunoglobulin and immunoreceptor tyrosine–based inhibitory motif (ITIM) domain (TIGIT) is specifically expressed in NK cells. This study aims to investigate the role of the TIGIT signaling pathway in regulating NK cell functions in patients with CHB.MethodWe comparatively assessed the expression of TIGIT in NK cells of patients with immune active CHB (CHB-IA), carriers of immune control chronic HBV (CHB-IC), and healthy controls (HCs), and then explored mechanisms of the TIGIT signaling pathway in regulating NK cell-mediated liver injury by different molecular assessments.ResultThe expression of TIGIT in NK cells was enhanced in CHB-IC but was reduced in CHB-IA compared with the HC group. In patients with CHB-IA, the expression of TIGIT was inversely correlated with intensity of the liver damage. Moreover, TIGIT-NK cells show higher IFN-γ secretion capability, degranulation activity, and cytotoxicity but lower apoptosis than TIGIT+ NK cells. Blockade of the TIGIT pathway with anti-TIGIT antibody increased NK cell function, while activation of the TIGIT pathway with TIGIT Fc and CD155 Fc chimera protein down-regulated NK cell function.ConclusionOur data showed that the TIGIT signaling pathway participates in NK cell impairment, which could be used as a new therapeutic target to protect patients with chronic HBV infection from severe liver injury.
COVI-Prim Longitudinal Survey: Experiences of Primary Care Physicians During the Early Phase of the COVID-19 Pandemic
Authors: Schaffler-Schaden Dagmar , Mergenthal Karola , Avian Alexander , Huter Sebastian , Spary-Kainz Ulrike , Bachler Herbert , Flamm Maria , Siebenhofer Andrea 
Published: February 2022

BackgroundGeneral practitioners (GPs) are the mainstay of primary care and play a critical role in pandemics. During the first wave of the COVID-19 pandemic, this international study aimed to explore changes in the workload of general practitioners, as well as their interactions with patients and colleagues, and their self-confidence and concerns.MethodsAn online survey was conducted among GPs in Austria and Germany. Participants were asked to answer a basic questionnaire and participate in a subsequent longitudinal survey containing closed and open-ended items. All data were pseudonymized.ResultsOverall, 723 general practitioners from Austria and Germany took part in the longitudinal survey over a period of 12 weeks (April 3–July 2, 2020). The majority of GPs had less direct contact with patients at the beginning of the survey (96 vs. 49% at the end of the study period). At first, doctors were mainly concerned with pandemic-related issues and had to care for the patients of GP colleagues that were in quarantine, which meant they had less time for routine work such as screenings and treating chronic diseases. Over the survey period, GPs' self-confidence increased and their concerns about income loss decreased.ConclusionsFollowing a difficult initial phase when protective equipment and information were lacking, physicians in primary care adapted quickly to new situations. Experience with telemedicine should help them face future challenges and may help prevent a decline in the delivery of routine health care and care for chronically ill patients.RegistrationTrial registration at the German Clinical Trials Register: DRKS00021231.
Pan-Cancer Analysis Identified CD93 as a Valuable Biomarker for Predicting Patient Prognosis and Immunotherapy Response
Authors: Tong Wen , Wang Guangyu , Zhu Liuyang , Bai Yi , Liu Zirong , Yang Long , Wu Hao , Cui Tao , Zhang Yamin 
Published: February 2022

Background: The rapid development of immunotherapy has significantly improved patient outcomes in recent years. CD93, a novel biomarker expressed on vascular endothelial cells, is essential for tumor angiogenesis. Recent studies have shown that CD93 is closely related to immune cell infiltration and immunotherapy. However, its role in pan-cancer has not been reported.Methods: The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), cbioportal, Gene Expression Omnibus (GEO), Tumor Immune Estimation Resource (TIMER2.0), and the Tumor–Immune System Interactions and Drug Bank (TISIDB) databases were used to analyze CD93 in pan-cancers. R software was used for statistical analysis and mapping.Results: There were significant differences in the expression of CD93 between tumor tissues and adjacent normal tissues in pan-cancer. The high expression of CD93 was associated with poor prognosis and high TNM stage in multiple tumor types. However, a high expression of CD93 was a protective factor in kidney renal clear cell carcinoma (KIRC). In addition, CD93 was closely related to immune cell infiltration in tumor tissues. Moreover, CD93 presented a robust correlation with immune modulators and immunotherapeutic markers [e.g., tumor mutation burden (TMB) and microsatellite instability (MSI)]. The results of gene set enrichment analysis (GSEA) showed that CD93 was correlated with tumor angiogenesis. Importantly, patients with a low expression of CD93 were more sensitive to immunotherapy in urothelial cancer.Conclusion: CD93, which is involved in various immune responses, controls immune cell infiltration and impacts on the malignant properties of various cancer types. Therefore, CD93 has potential value to be biomarker for determining the prognosis and immune infiltration in multiple cancers.
Prognosis and Survival Modelling in Cirrhosis Using Parenclitic Networks
Authors: Zhang Han , Oyelade Tope , Moore Kevin P. , Montagnese Sara , Mani Ali R. 
Published: February 2022

Background: Liver cirrhosis involves multiple organ systems and has a high mortality. A network approach to complex diseases often reveals the collective system behaviours and intrinsic interactions between organ systems. However, mapping the functional connectivity for each individual patient has been challenging due to the lack of suitable analytical methods for assessment of physiological networks. In the present study we applied a parenclitic approach to assess the physiological network of each individual patient from routine clinical/laboratory data available. We aimed to assess the value of the parenclitic networks to predict survival in patients with cirrhosis.Methods: Parenclitic approach creates a network from the perspective of an individual subject in a population. In this study such an approach was used to measure the deviation of each individual patient from the existing network of physiological interactions in a reference population of patients with cirrhosis. 106 patients with cirrhosis were retrospectively enrolled and followed up for 12 months. Network construction and analysis were performed using data from seven clinical/laboratory variables (serum albumin, bilirubin, creatinine, ammonia, sodium, prothrombin time and hepatic encephalopathy) for calculation of parenclitic deviations. Cox regression was used for survival analysis.Result: Initial network analysis indicated that correlation between five clinical/laboratory variables can distinguish between survivors and non-survivors in this cohort. Parenclitic deviations along albumin-bilirubin (Hazard ratio = 1.063, p &lt; 0.05) and albumin-prothrombin time (Hazard ratio = 1.138, p &lt; 0.05) predicted 12-month survival independent of model for end-stage liver disease (MELD). Combination of MELD with the parenclitic measures could predict survival better than MELD alone.Conclusion: The parenclitic network approach can predict survival of patients with cirrhosis and provides pathophysiologic insight on network disruption in chronic liver disease.
BDNF Val66Met Polymorphism Is Associated With Motor Recovery After Rehabilitation in Progressive Multiple Sclerosis Patients
Authors: Giordano Antonino , Clarelli Ferdinando , Cannizzaro Miryam , Mascia Elisabetta , Santoro Silvia , Sorosina Melissa , Ferrè Laura , Leocani Letizia , Esposito Federica 
Published: February 2022

BackgroundRehabilitation is fundamental for progressive multiple sclerosis (MS), but predictive biomarkers of motor recovery are lacking, making patient selection difficult. Motor recovery depends on synaptic plasticity, in which the Brain-Derived Neurotrophic Factor (BDNF) is a key player, through its binding to the Neurotrophic-Tyrosine Kinase-2 (NTRK2) receptor. Therefore, genetic polymorphisms in the BDNF pathway may impact motor recovery. The most well-known polymorphism in BDNF gene (rs6265) causes valine to methionine substitution (Val66Met) and it influences memory and motor learning in healthy individuals and neurodegenerative diseases. To date, no studies have explored whether polymorphisms in BDNF or NTRK2 genes may impact motor recovery in MS.ObjectivesTo assess whether genetic variants in BDNF and NTRK2 genes affect motor recovery after rehabilitation in progressive MS.MethodsThe association between motor recovery after intensive neurorehabilitation and polymorphisms in BDNF (rs6265) and NTKR2 receptor (rs2289656 and rs1212171) was assessed using Six-Minutes-Walking-Test (6MWT), 10-Metres-Test (10MT) and Nine-Hole-Peg-Test (9HPT) in 100 progressive MS patients.ResultsWe observed greater improvement at 6MWT after rehabilitation in carriers of the BDNF Val66Met substitution, compared to BDNF Val homozygotes (p = 0.024). No significant association was found for 10MT and 9HPT. NTRK2 polymorphisms did not affect the results of motor function tests.ConclusionBDNF Val66Met was associated with walking function improvement after rehabilitation in progressive MS patients. This result is in line with previous evidence showing a protective effect of Val66Met substitution on brain atrophy in MS. Larger studies are needed to explore its potential as a predictive biomarker of rehabilitation outcome.
Precision Medicine in Adult Obstructive Sleep Apnea and Home Diagnostic Testing: Caution in Interpretation of Home Studies Without Clinician Input Is Necessary
Authors: Do Timothy Quy-Phong , MacKay Stuart Grayson , Lam Matthew Eugene , Sideris Anders William , Jones Andrew Christopher , Chan Lyndon Sidney 
Published: February 2022

PurposeTo assess the validity of home sleep apnea test directed diagnosis and treatment of obstructive sleep apnea (OSA) in a real-life clinical setting and establish the extent to which clinical evaluation alters diagnosis and therapeutic intervention, in the context of the evolving realm of precision medicine.MethodsRetrospective consecutive cohort study of 505 patients referred to a single center between 15th September 2015 to 14th September 2016, multidisciplinary specialist sleep clinic presenting with a home sleep apnea test prior to referral. We evaluated the effect of sleep medicine practitioner (SMP) and ear, nose, and throat surgeon (ENTS) review on patient diagnoses, disease severity, and management options in OSA.ResultsHundred and fifteen patients were included. Repeat evaluation with in-lab polysomnogram (PSG) was required in 46/115 (40.0%) of patients, of which 20/46 (43.5%) had OSA severity changed. Sleep medicine practitioner review decreased the need for repeat testing with formal in-lab PSG (p &lt; 0.05) and increased patient acceptance of continuous positive airway pressure (CPAP) as a long-term management option for OSA. Sleep medicine practitioner/ENTS review resulted in discovery of a non-OSA related sleep disorder or change in OSA severity in 47.8% (55/115). Ear, nose, and throat surgeon review resulted in additional or changed diagnosis in 75.7% (87/115) of patients.ConclusionIn the clinical assessment and diagnosis of OSA, patients should be reviewed by medical practitioners with an interest in sleep disorders to better navigate the complexities of assessment, as well as the identification of co-morbid conditions.
The Mediating Roles of Family Resilience and Social Support in the Relationship Between Illness Severity and Depressive Symptoms Among Primary Caregivers of Children With Epilepsy in China
Authors: Wei Wenjing , Yang Rongrong , Zhang Jie , Chen Haili , Ye Jinghua , Su Qiru , Liao Jianxiang , Xiao Zhitian 
Published: February 2022

PurposeThis study was designed to assess the effects of epilepsy severity, family resilience, and social support on depression in primary caregivers of children with epilepsy (CWE), and to test the mediating roles of family resilience and social support in this relationship.MethodTwo hundred fifty-two caregivers of children with epilepsy were recruited from October 2020 to May 2021. The questionnaire contained sociodemographic characteristics, Epilepsy Severity, Chinese-Family Resilience Assessment Scale (C-FRAS), Social Support Rating Scale (SSRS), Beck Depression Inventory (BDI). Structural equation models were used to evaluate whether family resilience and social support as mediators between epilepsy severity and depression.ResultsIn this study, the prevalence of depressive symptoms among primary caregivers of CWE in China was 69.84%. Epilepsy severity was positively associated with depression. Family resilience and social support were negatively correlated with depressive symptoms (both p &lt; 0.01). Furthermore, the fitness indices of structural models were satisfactory. The direct effect of epilepsy severity on depression was 0.266 (95% CI 0.064–0.458), this pathway explained 62.88% variance of depression. The indirect effect of family resilience and then social support was 0.069 (95% CI 0.025–0.176), indicating that the serial multiple mediation was significant. The serial mediation pathway explained 16.31% variance of depression.ConclusionsThe high incidence of depression among primary carers of CWE deserves more attention. They should be screened routinely, especially those parents of children with severe epilepsy. Family resilience and social support could be protective factors for caregivers' mental adjustment. Therefore, future psychosocial interventions for enhancing family resilience and social support should be implemented, in order to reduce their depression.
Stroke Core Volume Weighs More Than Recanalization Time for Predicting Outcome in Large Vessel Occlusion Recanalized Within 6 h of Symptoms Onset
Authors: Ligot Noemie , Elands Sophie , Damien Charlotte , Jodaitis Lise , Sadeghi Meibodi Niloufar , Mine Benjamin , Bonnet Thomas , Guenego Adrien , Lubicz Boris , Naeije Gilles 
Published: February 2022

IntroductionCurrent guidelines suggest that perfusion imaging should only be performed &gt; 6 h after symptom onset. Pathophysiologically, brain perfusion should matter whatever the elapsed time. We aimed to compare relative contribution of recanalization time and stroke core volume in predicting functional outcome in patients treated by endovascular thrombectomy within 6-h of stroke-onset.MethodsConsecutive patients presenting between January 2015 and June 2021 with (i) an acute ischaemic stroke due to an anterior proximal occlusion, (ii) a successful thrombectomy (TICI &gt;2a) within 6-h of symptom-onset and (iii) CT perfusion imaging were included. Core stroke volume was automatically computed using RAPID software. Two linear regression models were built that included in the null hypothesis the pre-treatment NIHSS score and the hypoperfusion volume (Tmax &gt; 6 s) as confounding variables and 24 h post-recanalization NIHSS and 90 days mRS as outcome variables. Time to recanalization was used as covariate in one model and stroke core volume as covariate in the other.ResultsFrom a total of 377 thrombectomies, 94 matched selection criteria. The Model null hypothesis explained 37% of the variability for 24 h post-recanalization NIHSS and 42% of the variability for 90 days MRS. The core volume as covariate increased outcome variability prediction to 57 and 56%, respectively. Time to recanalization as covariate marginally increased outcome variability prediction from 37 and 34% to 40 and 42.6%, respectively.ConclusionCore stroke volume better explains outcome variability in comparison to the time to recanalization in anterior large vessel occlusion stroke with successful thrombectomy done within 6 h of symptoms onset. Still, a large part of outcome variability prediction fails to be explained by the usual predictors.
Severe Combined Immunodeficiency: Knowledge and Information Needs Among Healthcare Providers
Authors: Kutsa Oksana , Gwaltney Angela , Creamer Alissa , Raspa Melissa 
Published: February 2022

BackgroundSevere combined immunodeficiency (SCID) is a group of life-threatening genetic disorders responsible for severe dysfunctions of the immune system. Despite the expansion of newborn screening in the U.S., there are gaps in healthcare providers' knowledge of SCID.MethodsWe recruited 277 U.S. healthcare providers for an online survey. The survey assessed providers' experience with SCID patients, knowledge about SCID, and needs and preferred formats for SCID-related informational resources. We examined differences between providers who have seen 2 or more patients with SCID (SCID provider group) and those who have seen 0–1 SCID patients (non-SCID provider group).ResultsOverall, 210 (75.8%) providers were included in the non-SCID provider group, and 121 (57.6%) of these providers were pediatricians. Compared to the SCID provider group, non-SCID provider group reported lower mean rating of SCID knowledge (x̄ = 4.8 vs. x̄ = 8.6, p &lt; 0.0001) and higher informational needs. The largest informational needs identified by the non-SCID provider group were “understanding specific type of SCID” and “understanding what to expect across the lifespan.” In the SCID provider group, the highest rated informational need was “family support referrals.” Participants in the non-SCID provider group identified scientific publications and websites as preferred formats, with some variation between medical specialties.ConclusionBased on their experience with treating SCID patients, providers have varying levels of SCID knowledge and different informational needs. For providers who have encountered few SCID patients, informational needs start early, usually immediately after receiving a positive newborn screening result. These findings provide useful direction for the development and preferred outlets for receiving SCID-related information, with some variations between different types of providers. Results from this study will serve as a guide for creating relevant and accessible SCID resources for providers who can utilize them to improve care for SCID patients.