bluuebunny/crossref_metadata_2025_split huggingface dataset:
Seminal and testicular microbiome and male fertility
Authors: Brandão Pedro , Gonçalves-Henriques Manuel , Ceschin Nathan 
Published: December 2021

Abstract
Microbiome is of upmost importance for the well-being of the human body. Based on culture and PCR methods, seminal flora has been pointed as a potential cause for some of the unexplained male infertility.
This is a systematic review about the effect of seminal microbiota studied by Next Generation Sequencing techniques on sperm quality and male fertility, performed according to PRISMA statement.
Nine articles were included. Results of different studies are diverse. It seems that microbiota may a play a role in seminal quality and further male fertility, but the way this effect is modulated is still to be unknown. Lactobacillus spp seemed to play a beneficial role in semen quality, but the role of the remaining bacteria is unclear.
Due to the lack of research and the incongruence of the results so far, the effect of microbiota on seminal quality is still unclear.
MR-guided Cryoablation for the Treatment of Symptomatic Pedal Vascular Malformations
Authors: Knavel Koepsel Erica M. , Thompson Scott , Bendel Emily C. , Augustine Matthew , Tollefson Megha M. , Gorny Krzysztof R. , Lu Aiming , Favazza Christopher P. , Woodrum David A. 
Published: December 2021

Objective:
Vascular malformations are benign vascular anomalies characterized by abnormally developed arterial, venous, and lymphatic structures, which are often symptomatic. Historical and current treatment techniques include intravascular embolization/sclerosis and surgical resection. While these techniques have proven to be successful at managing and treating these types of lesions, these techniques are not without risk, especially in the small spaces of the hands and feet. Cryoablation for the treatment of low-flow vascular malformations is a new and evolving technique. We present five cases of symptomatic pedal vascular malformations treated with MR guided cryoablation, which provides encouraging safety and feasibility results for these difficult to treat lesions.

Methods:
A retrospective review of patients who had undergone MR-guided cryoablation of their pedal vascular malformations between January 2016 and January 2020 was performed.

Results:
Five cryoablations were completed without immediate complication. All patients reported markedly decreased pain corresponding to the treated area and improvement in their ability to return to a more active lifestyle. Two patients experienced mild transient numbness which resolved by 2–3 months and one patient experienced a transient motor and sensory neuropathy which resolved by 6 months.

Conclusion:
We present five cases of successful MR-guided cryoablation of symptomatic pedal venous malformations. Many of the patients included in this review failed conservative and other interventional/surgical treatments. The treatment options for this patient cohort can be limited given small space within the plantar aspect of the foot. Cryoablation of these lesions can be performed safely especially under continuous MRI monitoring.
Level of Evidence: Case series (Level 4)
SARC-F and other screening tests for sarcopenia
Authors: Bahat Gülistan , Erdoğan Tuğba , İlhan Birkan 
Published: December 2021

Purpose of review
Sarcopenia screening tools can enable clinicians to select individuals for more demanding evaluations, and hence, may facilitate its timely diagnosis and management. The most common recommended screening test is SARC-F, whereas many others are proposed. We aimed to summarize the recent studies and evidence performed on SARC-F and other sarcopenia screening tools.

Recent findings
Meta-analysis studies reported that despite having moderate-high specificity, SARC-F has low-moderate sensitivity to detect sarcopenia, which would cause a significant number of individuals having sarcopenia to be unrecognized. Several recent studies aimed to increase sensitivity and utility of SARC-F as a screening tool by i.e., application of lower cut-offs, adding extra-items, and combining with other screening tests. Some of these approaches increased its screening efficacy significantly. In line with its previous studies, SARC-F showed success to predict adverse outcomes in the latest studies as well. Recently, it has also been suggested as a reasonable screening test for frailty. In addition to the long-standing screening tests i.e., anthropometric measures, Ishii Test and Mini Sarcopenia Risk Assessment (MSRA) Questionnaire; new tests, i.e., Taiwan Risk Score for Sarcopenia, Sarcopenia Scoring Assessment Model (SarSA-Mod) and re-purposed tests, i.e., SARQoL questionnaire and fracture risk assessment tool have been investigated as potential screening tests for sarcopenia. Some of these tests performed as well as or superior to standard SARC-F.

Summary
Screening of sarcopenia is critical for public health given its significant prevalence and adverse outcomes. SARC-F is the most recommended tool for screening but has low-moderate sensitivity. Studies performed recently indicate that its sensitivity can be increased by some attempts and it may be used as a reasonable test to screen frailty as well. Some other tests have also been developed/re-purposed for an efficient screening, needing to be tested for their performance and usability with future studies in different populations and settings.
Successful treatment using immunotherapy in combination with chemotherapy for metastatic squamous cell carcinoma of unknown primary origin with bulky abdominal mass
Authors: Zhang Min , Zhao Meng , Jin Li-fang , Shen Wei-zhang 
Published: December 2021

Abstract

Rationale:
Cancer of unknown primary (CUP) means that the primary focus cannot be found after preliminary clinical evaluation. It accounts for 2.3% to 5% of newly diagnosed cancer cases. Due to the lack of standard treatment, CUP is usually associated with poor prognosis and is the third to fourth most common cause of cancer-related deaths.

Patient concerns:
We report the case of a 42-year-old female patient who was admitted to the hospital for intermittent right abdominal pain and abdominal distension. Abdominal computed tomography (CT) showed a large abdominal mass of unknown origin, which was difficult to resect due to its close relationship with surrounding tissues. Twenty days later, the patient had enlarged left supraclavicular lymph nodes, and percutaneous biopsy revealed squamous cell carcinoma. In addition, next-generation sequencing (NGS) of tissue and blood samples showed immune-related mutations and PD-L1 expression.

Diagnoses:
The patient was diagnosed with metastatic squamous cell carcinoma of unknown primary origin, with a bulky abdominal mass.

Interventions:
The patient was treated with carboplatin, albumin-binding paclitaxel, and immune checkpoint inhibitor (carilizumab). After 6 cycles, the patient was switched to maintenance treatment with carilizumab.

Outcomes:
The general condition of the patient improved, and the lesion was significantly reduced. The treatment efficacy was assessed as partial remission according to Response Evaluation Criteria in Solid Tumors. The patient benefited from immunotherapy combined with chemotherapy.

Lessons:
There is no recommended standard treatment for most CUPs, which leads to their poor prognoses. By performing NGS for patients and targeting immune-related positive predictors, immunotherapy combined with chemotherapy may prolong the overall survival of patients. This case report suggests that immunotherapy combined with chemotherapy is feasible and effective in patients with CUP.
Assessing aCCess to Investigations in Inflammatory Bowel Disease (ACCID): results from an international survey
Authors: Ding Nik S. , Lee Tanya , Bettenworth Dominik , Cleynen Isabelle , Yassin Nuha A. , Burisch Johan , Armuzzi Alessandro , Ferrante Marc , Zagorowicz Edyta , Mansfield John , Gesce Krisztina , Gisbert Javier P. , Raine Timothy 
Published: December 2021

Background
Multiple investigations are available to aid the diagnosis and monitoring of disease activity in inflammatory bowel disease (IBD). Fecal calprotectin (FC) is an established surrogate for intestinal inflammatory activity. Therapeutic drug monitoring (TDM) including thiopurine metabolites, anti-tumor necrosis factor (TNF) levels and antidrug antibody measurements are a step toward personalized medicine in IBD, but face access barriers. We aimed to assess test availability and barriers for these investigations in European practice.

Methods
Five-hundred questionnaires were distributed to workshop participants at the 11th Congress of the European Crohn’s and Colitis Organisation (ECCO). Access to FC, TDM for thiopurines and anti-tumor necrosis factor agents, as well as factors associated with usage and barriers to access were recorded.

Results
Responses were obtained from 195 attendees from 38 countries across a range of practices, healthcare settings and levels of experience. FC was available to 92.3% while access to anti-TNF (78.9%, P = 0.02 vs.  thiopurine TDM, P = 0.0002 vs.  FC) and thiopurine TDM (67.7%, P = 0.0001) were less widespread. Cost was a frequently cited barrier to test access or usage, with access having a significant West–East and North–South divide across all three investigations. The strongest independent predictor of access to all tests was healthcare spending per capita (P = 0.005 for FC; P < 0.0001 for both TDM).

Conclusion
FC, anti-TNF and thiopurine TDM are increasingly incorporated as part of routine practice in IBD care across Europe and have the potential to impact positively on patient care. However, access barriers remain of which we found test cost the most significant with the investment required to reduce these barriers.
Effects of naringenin supplementation on cardiovascular risk factors in overweight/obese patients with nonalcoholic fatty liver disease: a pilot double-blind, placebo-controlled, randomized clinical trial
Authors: Naeini Fatemeh , Namkhah Zahra , Tutunchi Helda , Rezayat Seyed Mahdi , Mansouri Siavash , Yaseri Mehdi , Hosseinzadeh-Attar Mohammad Javad 
Published: December 2021

Objective
Although several experimental models have suggested promising pharmacological effects of naringenin in the management of obesity and its related disorders, the effects of naringenin supplementation on cardiovascular disorders as one of the main complications of nonalcoholic fatty liver disease (NAFLD) are yet to be examined in humans.

Methods
In this double-blind, placebo-controlled, randomized clinical trial, 44 overweight/obese patients with NAFLD were equally allocated into either naringenin or placebo group for 4 weeks. Cardiovascular risk factors including atherogenic factors, hematological indices, obesity-related parameters, blood pressure, and heart rate were assessed pre- and postintervention.

Results
The atherogenic index of plasma value, serum non-HDL-C levels as well as total cholesterol/high-density lipoprotein cholesterol (HDL-C), triglyceride/HDL-C, low-density lipoprotein cholesterol/HDL-C, and non-HDL-C/HDL-C ratios were significantly reduced in the intervention group, compared to the placebo group post intervention (P < 0.05). Moreover, there was a significant reduction in BMI and visceral fat level in the intervention group when compared with the placebo group (P = 0.001 and P = 0.039, respectively). Furthermore, naringenin supplementation could marginally reduce systolic blood pressure (P = 0.055). Mean corpuscular hemoglobin increased significantly in the naringenin group compared to the placebo group at the endpoint (P = 0.023). Supplementation with naringenin also resulted in a marginally significant increase in the mean corpuscular hemoglobin concentration when compared with the placebo group (P = 0.050). There were no significant between-group differences for other study outcomes post intervention.

Conclusion
In conclusion, these data indicate that naringenin supplementation may be a promising treatment strategy for cardiovascular complications among NAFLD patients. However, further trials are warranted.
Safety of Irreversible Electroporation Ablation of the Pancreas
Authors: Lee Edward Wolfgang , Shahrouki Puja , Peterson Stephanie , Tafti Bashir A. , Ding Peng-Xu , Kee Stephen T. 
Published: December 2021

Objectives
To evaluate the safety of irreversible electroporation (IRE) on swine pancreatic tissue including its effects on peripancreatic vessels, bile ducts, and bowel.

Methods
Eighteen Yorkshire pigs underwent IRE ablation of the pancreas successfully and without clinical complications. Contrast-enhanced computed tomography angiography and laboratory studies before the IRE ablation with follow-up computed tomography angiography, laboratory testing, and pathological examination up to 4 weeks postablation were performed.

Results
In a subset of cases, anatomic peripancreatic vessel narrowing was seen by 1 week postablation, persisting at 4 weeks postablation, without apparent functional impairment of blood flow. Laboratory studies revealed elevated amylase and lipase at 24 hours post-IRE, suggestive of acute pancreatitis, which normalized by 4 weeks post-IRE. There was extensive pancreatic tissue damage 24 hours after IRE with infiltration of immune cells, which was gradually replaced by fibrotic tissue. Ductal regeneration without loss of pancreatic acinar tissue and glandular function was observed at 1 and 4 weeks postablation.

Conclusions
In our study, we demonstrated and confirmed the safety and minimal complications of IRE ablation in the pancreas and its surrounding vital structures. These results show the potential of IRE as an alternative treatment modality in patients with pancreatic cancer, especially those with locally advanced disease.
Reduced Free Fatty Acid Receptor 4 Gene Expression is Associated With Extreme Obesity and Insulin Resistance in Children
Authors: Codoñer‐Alejos Alan , Carrasco‐Luna Joaquín , Carrasco‐García Álvaro , Codoñer‐Franch Pilar 
Published: December 2021

ABSTRACTObjectives:Free fatty acid receptor 4 (FFAR4) is a G‐protein‐coupled membrane receptor highly expressed in macrophages that triggers anti‐inflammatory effects and promotes insulin sensitization. We have previously found significant associations between the FFAR4 rs11187533 single nucleotide polymorphism (SNP) and various obesity comorbidity parameters. We aimed to verify the FFAR4 expression levels in children with obesity and the associated comorbidities.Methods:Thirty‐eight children with obesity were studied. Clinical and anthropometric evaluation was performed. A venous sample under fasting conditions was obtained. Biochemical study included parameters of metabolic risk. DNA was extracted and genotyped for the rs11187533 FFAR4 SNP. Real‐time PCR technique was performed to investigate the gene expression. Relative FFAR4 mRNA levels were determined according to the 2−ΔΔCt method.Results:Significant differences in FFAR4 expression levels between the CC and CT‐TT genotypes of the rs11187533 FFAR4 SNP were observed (P = 0.034). The minor allele T presented higher levels of FFAR4 expression. We found that a loss of FFAR4 expression was associated with extreme obesity (P = 0.032). The lowest FFAR4 expression levels were observed in children who had higher insulin (P = 0.008) and homeostasis model assessment insulin resistance values (P = 0.012) and lower quantitative insulin‐sensitivity check index (P = 0.033).Conclusions:The underexpression of FFAR4 was associated with extreme obesity and parameters indicative of obesity comorbidities in children. This under expression could be partially influenced by the presence of the C allele rs11187533 FFAR4 SNP.
Clinical Implications for Children Developing Direct Hyperbilirubinemia on Extracorporeal Membrane Oxygenation
Authors: Alexander Erin , O'Sullivan Donnchadh , Aganga Devon , Hassan Sara , Ibrahim Samar H. , Absah Imad 
Published: December 2021

ABSTRACTObjective:Extracorporeal membrane oxygenation (ECMO)‐associated direct hyperbilirubinemia (DHB) is likely multifactorial. The objective of this study is to assess the frequency and risk factors for developing direct hyperbilirubinemia while on ECMO, and its implication on the mortality of children.Methods:We performed a retrospective study between January 2010 and January 2020. Using Mayo Clinic electronic health record, we identified children (<18 years) who required veno‐arterial (VA) ECMO support. Demographics, ECMO indication, laboratory findings, and outcomes were abstracted. Illness acuity scores, including vasoactive‐ionotropic score (VIS), were used to assess disease severity at time of admission. Study cohort was divided into two groups: children who developed direct hyperbilirubinemia (DHB) on ECMO and children who did not (control). DHB was defined as direct bilirubin (DB) of >1.0 mg/dL. Disease acuity and mortality rates were compared between the two groups. Logistic regression was used to analyze the risk of mortality independent of potential confounding variables.Results:We identified 106 children who required ECMO support during the study period. Of those, 36 (34%) children developed DHB on ECMO. Illness acuity scores were significantly higher in the DHB group on ECMO day 2 (P = 0.046) and day 7 (P = 0.01). Mortality rate was higher in the DHB group 72%, versus 29% in the control group (P < 0.001).Conclusion:DHB was associated with a higher mortality rate than the control group.
Long‐Term Outcomes With Adalimumab Therapy in Pediatric Crohn Disease
Authors: Rinawi Firas , Popalis Cynthia , Tersigni Claudia , Frost Karen , Muise Aleixo , Church Peter C. , Walters Thomas D. , Ricciuto Amanda , Griffiths Anne M. 
Published: December 2021

ABSTRACTBackground/Aims:Pediatric Crohn disease (CD) treatment goals have evolved. Among children receiving adalimumab (ADA) we examined long‐term durability of clinical remission, linear growth, and associations of trough concentration (TC) with biomarker, endoscopic and imaging outcomes.Methods:Single‐center retrospective study. Pediatric CD activity index, C‐reactive protein, fecal calprotectin, and height measured longitudinally. Discontinuation due to secondary loss of response (LOR) was assessed using Cox proportional hazards model. Associations between TC and clinical and biomarker remission, endoscopic and magnetic resonance imaging (MRI) improvements were assessed using Cox regression with time‐dependent covariates.Results:Between January 2007 and June 2018, 213 children (median age 14.1 years (interquartile range [IQR] 12.5–15.7) 65% males) initiated ADA. One hundred and seventy‐four (82%) achieved clinical remission (PCDAI < 10). During 24.8 (IQR 15.6–38.4) months follow‐up, 26 (15%) discontinued ADA due to LOR, and 10 (6%) due to adverse events. Being anti‐tumor necrosis factor (TNF) naïve and inflammatory behavior associated with increased likelihood of clinical remission (odds ratio [OR] 2.39, P = 0.033, and 3.13, P = 0.013, respectively) and with decreased LOR (hazard ratio [HR] 0.3, P = 0.002, and HR 0.35, P = 0.01, respectively). Cumulative LOR among 135 anti‐TNF naïve patients: 0%, 8%, 15% within 1, 2, 3 years, similarly durable with mono‐ and immunomodulator combination therapy. Among pre‐/early pubertal children mean height (−0.82) normalized to −0.07. TC consistently >7.5 ug/mL was associated with durable clinical remission (HR = 17.24, P < 0.001); TC >10 ug/mL with durable biomarker remission (HR = 6.56, P < 0.001) and endoscopic (OR 10.4, P = 0.002) and MRI (OR 7.6, P = 0.001) improvements.Conclusion:ADA monotherapy maintains durable clinical remission. Biomarker remission, mucosal and transmural improvements were associated with greater ADA exposure.
Growth patterns of uninfected children born to women living with perinatally versus nonperinatally acquired HIV
Authors: Yu Wendy , Jacobson Denise L. , Williams Paige L. , Patel Kunjal , Geffner Mitchell E. , Van Dyke Russell B. , Kacanek Deborah , DiMeglio Linda A. , Jao Jennifer 
Published: December 2021

Objective:
The aim of this study was to compare long-term growth between HIV-exposed uninfected children (CHEU) born to women with perinatally acquired HIV (CHEU-PHIV) and CHEU born to women with nonperinatally acquired HIV (CHEU-NPHIV).

Design:
A longitudinal analysis of anthropometric measurements from a U.S.-based multisite prospective cohort study enrolling CHEU and their mothers since April 2007.

Methods:
CHEU were evaluated for growth annually from birth through age 5 and again at age 7 years. Z-scores were calculated using U.S. growth references for weight (WTZ), height (HTZ), and weight-for-length or BMI-for-age (WLZ/BMIZ). Mid-upper arm circumference (MUACZ) and triceps skinfold thickness (TSFZ) Z-scores were obtained from ages 1 and 2, respectively, through age 7 years. Piecewise mixed-effects models, overall and stratified by race and sex, were fit to assess differential growth patterns across age by maternal PHIV status.

Results:
One thousand four hundred fifty-four singleton infants (286 CHEU-PHIV and 1168 CHEU-NPHIV) were included. CHEU-PHIV had slower growth rates than CHEU-NPHIV for WTZ and WLZ/BMIZ at earlier ages and continued to have lower mean WTZ [−0.27, 95% confidence interval (95% CI): −0.50, −0.04] and WLZ/BMIZ (−0.39, 95% CI: −0.67, −0.11) through age 7. Among non-Black boys, CHEU-PHIV had slightly lower WTZ and WLZ/BMIZ at birth than CHEU-NPHIV and these growth deficits persisted through age 7 years.

Conclusion:
Compared with CHEU-NPHIV, CHEU-PHIV had diminished growth in early childhood with differences most pronounced among non-Black male children. Further longitudinal follow-up of CHEU-PHIV into young adulthood is needed to understand whether these early effects of maternal PHIV status on growth persist and have other health consequences.
Quantitative Analysis of Radial Peripapillary Capillary Network in Patients With Papilledema Compared with Healthy Subjects Using Optical Coherence Tomography Angiography
Authors: Chonsui Moerani , Le Goff Mélanie , Korobelnik Jean-François , Rougier Marie-Bénédicte 
Published: December 2021

Background:
To quantitatively compare the peripapillary microvascular network between patients with papilledema and healthy subjects using swept source optical coherence tomography angiography.

Methods:
In this retrospective observational study, patients with papilledema secondary to idiopathic intracranial hypertension and healthy controls were imaged with swept source optical coherence tomography angiography (PLEX Elite 9000; Carl Zeiss Meditec, Dublin, CA) using a 6 × 6 mm scan pattern centered on the optic disc. The capillary perfusion density (CPD) and capillary flux index (CFI) of the radial peripapillary capillaries in the retinal nerve fiber layer (RNFL) were calculated using Zeiss algorithm.

Results:
Thirty-nine eyes of 20 patients with papilledema and 66 eyes of 33 healthy subjects were imaged. The mean (P < 0.01), superior (P < 0.01), inferior (P < 0.01), and temporal (P = 0.02) CPD significantly differed between both groups. No significant difference was found between both groups for the CFI. The mean (P < 0.01), superior (P < 0.01), inferior (P = 0.01), temporal (P < 0.01), and nasal (P < 0.01) quadrants of the RNFL were positively associated with the CFI. The mean (P < 0.01), superior (P = 0.01), inferior (P = 0.01), temporal (P < 0.01), and nasal (P = 0.01) quadrants of the RNFL were negatively associated with the CPD.

Conclusion:
Our study showed a decreased peripapillary capillary density without changes in flux intensity in eyes with papilledema. There were a positive association between the CFI and the RNFL and a negative association between the CPD and the RNFL. It confirmed the discriminatory ability of OCTA in differentiating a papilledema secondary to IIH from a normal optic disc, while providing complementary information for understanding papilledema pathophysiology.