bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stromal vascular fraction with platelet‐rich plasma injection during surgery is feasible and safe in treatment‐refractory perianal fistulising Crohn's disease: A pilot study
Authors: Arkenbosch Jeanine H. C. , van Ruler Oddeke , Dwarkasing Roy S. , Fuhler Gwenny M. , Schouten W. Rudolph , van Oud‐Alblas Marjolein Blussé , de Graaf Eelco J. R. , de Vries Annemarie C. , van der Woude C. Janneke 
Published: December 2022

SummaryBackgroundAn unmet need remains for improved management in perianal fistulising Crohn's disease (pCD). Recently, local administration of adipose‐derived cells has shown promising results.AimsTo assess the safety and feasibility of injection of stromal vascular fraction (SVF) with platelet‐rich plasma (PRP) in patients with pCD.MethodsPatients ≥ 18 years with pCD were included and underwent fistula curettage, SVF with PRP injection, and closure of the internal opening. The primary endpoint was safety at 12 months. The secondary outcomes were complete radiological healing at 3 months (absence of fluid‐containing tracts on MRI) and partial and complete clinical response at 3 and 12 months (closure of ≥1, respectively, all treated external opening(s)).ResultsTwenty‐five patients were included (35 [IQR 25–40] years; 14 [56%] female); median CD duration 4 [IQR 2–8] years. Twenty‐four (95%) patients had previously undergone fistula surgery. No adverse events were encountered at lipoharvesting sites. Two (8%) patients were readmitted to hospital and six (24%) underwent unplanned re‐interventions. Post‐operative MRI (n = 24) showed complete radiological healing in nine (37.5%) patients. Partial clinical response was present in 48% (12/25) at 3 months and in 68% (17/25) at 12 months, and complete clinical closure in five (20%) patients at 3 months and in 10 (40%) patients at 12 months.ConclusionInjection with autologous SVF with PRP is feasible and safe in patients with treatment‐refractory pCD. Early complete radiological healing was observed in more than one‐third of patients, and clinical response in two‐thirds of patients at 12 months.
Dissection of the autophagic route in oocytes from atretic follicles
Authors: Castro‐Cruz Abraham , Echeverría Olga M. , Sánchez‐Sánchez Luis , Muñoz‐Velasco Israel , Juárez‐Chavero Silvia , Torres‐Ramírez Nayeli , Vázquez‐Nin Gerardo H. , Escobar María Luisa 
Published: December 2022

AbstractBackground InformationAutophagy is a conserved process that functions as a cytoprotective mechanism; it may function as a cell death process called programmed cell death type II. There is considerable evidence for the presence of autophagic cell death during oocyte elimination in prepubertal rats. However, the mechanisms involved in this process have not been deciphered.ResultsOur observations revealed autophagic cell death in oocytes with increased labeling of the autophagic proteins Beclin 1, light chain 3 A (LC3 A), and lysosomal‐associated membrane protein 1 (Lamp1). Furthermore, mTOR and phosphorylated (p)‐mTOR (S2448) proteins were significantly decreased in oocytes with increased levels of autophagic proteins, indicating autophagic activation. Moreover, phosphorylated protein kinase B (p‐AKT) was not expressed by oocytes, but mitogen‐activated protein kinase/extracellular signalregulated kinase (MAPK/ERK) signaling was observed. Additionally, selective and elevated mitochondrial degradation was identified in altered oocytes.ConclusionsAll these results suggest that mTOR downregulation, which promotes autophagy, could be mediated by low energy levels and sustained starvation involving the phosphoinositide 3‐kinase (PI3K)/AKT/mTOR and MAPK/ERK pathways.SignificanceIn this work, we analyzed the manner in which autophagy is carried out in oocytes undergoing autophagic cell death by studying the behavior of proteins involved in different steps of the autophagic pathway.
Single‐cell next‐generation sequencing of circulating tumor cells in patients with neuroblastoma
Authors: Kojima Masato , Harada Takanori , Fukazawa Takahiro , Kurihara Sho , Touge Ryo , Saeki Isamu , Takahashi Shinya , Hiyama Eiso 
Published: December 2022

AbstractCirculating tumor cells (CTCs) derived from any tumor tissue could contribute to metastasis and resistance to cancer treatments. In this study, we performed single‐cell next‐generation sequencing of CTCs and evaluated their usefulness for characterizing tumor biology and the mechanisms of metastasis in neuroblastomas (NB). We aimed to isolate CTCs from 10 patients with NB at diagnosis before any treatments and four patients at relapse. GD2+CD90+CD45−CD235a−DAPI− cells were isolated as neuroblastoma CTCs using fluorescence‐activated cell sorting. In five patients with advanced stages (M stage), DNA and RNA sequencing of CTCs at single‐cell level were performed. NB CTCs were isolated from eight of the 10 patients at diagnosis and three of the four patients at relapse. More CTCs could be isolated from patients with advanced stages. In one patient, ALK mutation (p.F1174L), was identified in both tumor tissue and a CTC. In patients with MYCN amplification, this gene was amplified in 12 of 13 CTCs. Using single‐cell RNA sequencing, angiogenesis‐related and cell cycle‐related genes together with CCND1 and TUBA1A genes were found to be upregulated in CTCs. In one patient, CTCs were divided into two subgroups showing different gene expression profiles. In one subgroup, cell cycle‐related and proliferation‐related genes were differentially upregulated compared with the other group. In conclusion, next‐generation sequencing of CTCs at single‐cell level might help to characterize the tumor biology and the mechanisms of metastasis in NB.
High prevalence of coronary artery calcification and increased risk for coronary artery disease in patients with Sheehan syndrome—A case–control study
Authors: Laway Bashir Ahmad , Rasool Abid , Baba Mohammad Salem , Misgar Raiz Ahmad , Bashir Mir Iftikhar , Wani Arshad Iqbal , Choh Naseer , Shah Omair , Lone Ajaz , Shah Zaffar 
Published: December 2022

AbstractObjectivePatients with Sheehan syndrome (SS) are predisposed to coronary artery disease (CAD) due to risk factors like abdominal obesity, dyslipidemia and chronic inflammation. In addition to estimate CAD risk enhancers like high sensitive C reactive protein (hsCRP), apolipoprotein B (ApoB) and lipoprotein A [Lp(a)], this study applies Framingham risk score (FRS) and coronary artery calcium (CAC) score to compute a 10‐year probability of cardiovascular (CV) events in SS patients.DesignCase–control study Sixty‐three SS patients, on a stable hormonal replacement treatment except for growth hormone and 65 age, body mass index and parity‐matched controls.MeasurementsMeasurement of serum hsCRP, ApoB and Lp(a) and estimation of CAC with 16‐row multislice computed tomography scanner.ResultsThe concentrations of hsCRP, ApoB and Lp(a) were significantly higher in SS patients than in controls (p < .01). After calculating FRS, 95.2% of SS patients were classified as low risk, 4.8% as intermediate risk and all controls were classified as low risk for probable CV events. CAC was detected in 50.7% SS patients and 7.6% controls (p = .006). According to the CAC score, 26.9% SS patients were classified as at risk (CAC > 10) for incident CV events as against 1.6% controls. The mean Multi‐Ethnic Study of Atherosclerosis (MESA) score was significantly higher in patients with SS than controls. CAC corelated significantly with fasting blood glucose (r = .316), ApoB (r = .549), LP(a) (r = .310) and FRS (r = .294).ConclusionSignificant number of asymptomatic SS patients have high coronary artery calcium score and are classified at risk for CAD.
Spectral‐domain optical coherence tomography biomarkers in vitreoretinal lymphoma
Authors: Guan Wenxue , Xiao Yuanyuan , Zhao Huiying , Hu Feng , Chen Chunli , Peng Xiaoyan 
Published: December 2022

AbstractBackgroundAlthough early detection is critical, diagnosing vitreoretinal lymphoma (VRL) remains difficult. We sought to assess the potential diagnostic value of spectral‐domain optical coherence tomography (SD‐OCT) in VRL.MethodsWe reviewed the clinical records and pre‐treatment SD‐OCT images of biopsy‐confirmed VRL and uveitis patients, with primary involvement of the sub‐retinal pigment epithelium (RPE) and the outer retina, including acute syphilitic posterior placoid chorioretinitis (ASPPC), chronic stage sympathetic ophthalmitis (SO), and idiopathic multifocal choroiditis (MFC).ResultsWe included 45 eyes of 45 VRL patients and 40 eyes of 40 uveitis patients (17 ASPPC eyes, eight chronic SO eyes, and 15 MFC eyes). On SD‐OCT, lymphoma cell infiltration was observed in various retinal layers, most commonly in the sub‐RPE (80%) and sub‐retinal space (62%). Highly sensitive features for VRL as compared to uveitis included vitreous cells (93%), focal hyper‐reflective sub‐retinal infiltration (51%), and diffuse RPE elevations (56%). The features strongly specific for VRL included preretinal deposits (92.5%), intra‐retinal infiltration (except the incomplete vertical hyper‐reflective type, 100%), banded hyper‐reflective sub‐retinal infiltration (90%), and confluent RPE detachments (100%). We identified an approach to VRL diagnosis based on these SD‐OCT findings: (1) two highly sensitive features plus one strongly specific feature; or (2) one highly sensitive feature plus two strongly specific features, demonstrated a sensitivity of 80% and specificity of 95% for VRL.ConclusionsThe SD‐OCT may enable the detection of detailed lymphoma infiltration characteristics and provide significant supplemental value for VRL diagnosis, particularly when combining highly sensitive and specific VRL‐associated SD‐OCT features.
Short‐ and long‐term outcomes following bridge to surgery and emergency resection in acute malignant large bowel obstruction
Authors: Arnarson Örvar , Axmarker Tobias , Syk Ingvar 
Published: December 2022

AbstractAimBridge to surgery (BtS) aims to decrease perioperative morbidity and mortality in emergency resection (ER) of the colon. Previous results are inconsistent, and long‐term comparisons are scarce. The aim of this study was to compare the short‐ and long‐term outcomes of BtS and ER.MethodThis retrospective study examined data from the Swedish Colorectal Cancer Registry for patients treated for acute malignant large bowel obstruction from 2007 to 2009. Patients were grouped by treatment strategy: BtS (using a self‐expanding metallic stent or diverting stoma) or ER. Medical records were scrutinized for all patients in the BtS group. The primary endpoints were 5‐year overall survival (OS) and 3‐year recurrence‐free survival (RFS). The secondary endpoints were postoperative mortality and morbidity rates and stoma permanence.ResultsOverall, 143 patients were treated using BtS versus 1302 patients treated with ER. The 5‐year OS was higher in the BtS group than in the ER group (53.8% vs. 37.4%; p < 0.05). No difference was noted in the 3‐year RFS (75.7% vs. 75.0%; p = 0.38). The postoperative mortality rate was lower in the BtS group than in the ER group (0.7% vs. 7.3%; p < 0.05). Complications occurred in 46.9% of patients in the BtS group (both procedures) versus 35.9% of patients in the ER group (p < 0.05); the rate of severe complications was 23.1% and 16.9%, respectively (p = 0.07).ConclusionThis retrospective population‐based registry study showed higher long‐term survival and lower postoperative mortality rates among patients treated with BtS versus ER for acute malignant large bowel obstruction.
Higher number of tacrolimus dose adjustments in kidney transplant recipients who are extensive and intermediate CYP3A5 metabolizers
Authors: Reininger Kevin A. , Onyeaghala Guillaume , Anderson‐Haag Teresa , Schladt David S. , Wu Baolin , Guan Weihua , Dorr Casey R. , Remmel Rory P. , Mannon Roslyn , Matas Arthur J. , Oetting William S. , Stahler Paul , Israni Ajay K. , Jacobson Pamala A. 
Published: December 2022

AbstractKidney transplant recipients carrying the CYP3A5*1 allele have lower tacrolimus troughs, and higher dose requirements compared to those with the CYP3A5*3/*3 genotype. However, data on the effect of CYP3A5 alleles on post‐transplant tacrolimus management are lacking. The effect of CYP3A5 metabolism phenotypes on the number of tacrolimus dose adjustments and troughs in the first 6 months post‐transplant was evaluated in 78 recipients (64% Caucasians). Time to first therapeutic concentration, percentage of time in therapeutic range (TTR), and estimated glomerular filtration rate (eGFR) were also evaluated. Fifty‐five kidney transplant recipients were CYP3A5 poor metabolizers (PM), 17 were intermediate metabolizers (IM), and 6 were extensive metabolizers (EM). Compared to PMs, EMs/IMs had significantly more dose adjustments (6.1 vs. 8.1, p = .015). Overall, 33.82% of trough measurements resulted in a dose change. There was no difference in the number of tacrolimus trough measurements between PMs and EM/IMs. The total daily tacrolimus dose requirements were higher in EMs and IMs compared to PMs (<.001). TTR was ∼50% in the PMs and EMs/IMs groups. CYP3A5 EM/IM metabolizers have more tacrolimus dose changes and higher dose requirements which increases clinical management complexity. Larger studies are needed to assess the cost and benefits of including genotyping data to improve clinical management.
Clinicopathological features of atypical glandular cells, not otherwise specified, on cervicovaginal pap smears
Authors: Aytekin Okan , Cakir Caner , Unsal Mehmet , Celik Fatih , Tokalioglu Abdurrahman Alp , Kilic Fatih , Ersak Burak , Codal Bahadır , Kahraman Alper , Gokkaya Mustafa , Ayhan Sevgi , Akar Serra , Cesur Nesibe , Erdogan Fazli , Ozdal Bulent , Oktar Okan , Koc Sevgi , Boran Nurettin , Comert Gunsu Kimyon , Ureyen Isin , Toptas Tayfun , Korkmaz Vakkas , Ustun Yaprak , Tekin Ozlem Moraloglu , Turkmen Osman , Turan Taner 
Published: December 2022

AbstractObjectiveThe Papanicolaou (Pap) smear test is a standard screening test that detects cervical lesions and cancers. In this multicentric study, we performed a retrospective analysis of cytological results associated with atypical glandular cells, not otherwise specified (AGC‐NOS).MethodsWe retrospectively reviewed Pap smear tests that resulted as AGC‐NOS. A total of 254 women who underwent colposcopy due to a Pap smear result of AGC‐NOS were included the study between 2003 and 2021. The ages, Pap smear results, HPV results if any, colposcopic biopsy results, endocervical and endometrial pathology results, and management of these patients were analysed.ResultsTwo hundred fifty‐four patients with AGC‐NOS Pap smear results were included in the study. A total of 70 (27.6%) patients had cervical and endometrial premalignant or malignant lesions. Malignancy was observed in 17 (6.7%) patients (endometrium, n = 11 [4.3%]; cervix, n = 6 [2.4%]). Isolated premalignant or malignant lesions of the cervix and endometrium were detected in 57 (22.4%) and 12 (4.7%) patients, respectively.ConclusionsPatients diagnosed with AGC‐NOS should undergo a careful evaluation with all clinicopathological features. Because cancer of the cervix and endometrium is not rare in patients diagnosed with AGC‐NOS, colposcopic examination with endocervical sampling should be a priority based on a cervicovaginal smear. Endometrial sampling is also required according to the patient's clinic, age, and examination characteristics.
Efficacy and tolerability of 1 L polyethylene glycol plus ascorbic acid with senna versus 2 L polyethylene glycol plus ascorbic acid for colonoscopic bowel preparation: Prospective, randomized, investigator‐blinded trial
Authors: Maeda Natsumi , Higashimori Akira , Nakatani Masami , Jinnai Kagami , Kin Daiyu , Sugita Naoko , Morimoto Kenichi , Sasaki Eiji , Fukuda Takashi , Fujiwara Yasuhiro 
Published: December 2022

ObjectivesLow‐volume polyethylene glycol plus ascorbic acid (PEG‐Asc) reduces the dosage of colonoscopic bowel preparation (BP) solution, but is still poorly tolerated. Adding laxatives to the BP solution reduces the volume of fluid required, without affecting quality. This study aimed to compare 1 L PEG‐Asc plus 24 mg senna (1L‐PEG/AS) and conventional 2 L PEG‐Asc (2L‐PEG/A) regimens on BP quality and patient tolerability.MethodsA single‐center, randomized, investigator‐blinded, noninferiority trial was performed between June and August 2022. Outpatients scheduled for colonoscopy were randomized (1:1) to the 1L‐PEG/AS or 2L‐PEG/A group. The Boston Bowel Preparation Scale (BBPS) was used to evaluate BP quality. Adverse events and tolerability were surveyed using questionnaires.ResultsOverall, 344 patients received 1L‐PEG/AS or 2L‐PEG/A regimens. The baseline characteristics and adverse events of the two groups were comparable. The 1L‐PEG/AS group showed noninferior adequate BP rates compared with the 2L‐PEG/A group (88% vs. 89%, P = 1.00); overall BBPS was 7.1 ± 1.5 and 7.2 ± 1.5, respectively (P = 0.39). Higher willingness to repeat the BP was observed in the 1L‐PEG/AS group (85% vs. 62%, P < 0.01).ConclusionsThe 1L‐PEG/AS regimen was comparable to the 2L‐PEG/A regimen in terms of BP adequacy, requiring lower BP solution volumes, with better patient tolerance. Thus, it may be a suitable alternative to the conventional BP solution for colonoscopy.The Japan Registry of Clinical Trials (jRCT1051220043).
Development and validation of a prediction model for histologic progression in patients with nondysplastic Barrett's esophagus
Authors: Peleg Noam , Ringel Yehuda , Shamah Steven , Schmilovitz‐Weiss Hemda , Leshno Moshe , Benjaminov Fabiana , Shinhar Nadav , Gingold‐Belfer Rachel , Dotan Iris , Sapoznikov Boris 
Published: December 2022

ObjectivesPatients with Barrett's esophagus (BE) are at risk of progression to esophageal adenocarcinoma (EAC). We developed a model to predict histologic progression in patients with nondysplastic BE (NDBE).MethodsA longitudinal study in three referral centers was performed between January 2010 and December 2019. As progression to low‐grade dysplasia (LGD) can be considered an indication for ablative therapy, the study end‐point was histopathologic progression to LGD, high‐grade dysplasia, or EAC at 3 years after diagnosis. We used logistic regression to create the model. Seventy percent of the cohort were used to stem the model and the remaining 30% for internal validation.ResultsA total of 542 patients were included, 69.4% of whom were male, mean age 62.2 years. Long‐segment BE at index endoscopy was diagnosed in 20.8% of the patients. After a mean follow‐up of 6.7 years, 133 patients (24.5%) had histologic progression. Our model identified a neutrophil‐to‐lymphocyte ratio (odds ratio [OR] 2.08, 95% confidence interval [CI] 1.77–2.32, P < 0.001), BE length (OR 1.22, 95% CI 1.09–1.36, P < 0.001), age (OR 1.03, 95% CI 1.02–1.05, P = 0.02), smoking (OR 1.66, 95% CI 1.09–2.75, P = 0.04), and renal failure (OR 1.51, 95% CI 0.93–2.43, P = 0.07) as predictors of histologic progression at 3 years. The areas under the receiver operating characteristic curves of this model were 0.88 and 0.76 in the training and validation cohorts, respectively.ConclusionThis novel, internally validated model may predict histologic progression, even in patients with NDBE who generally have low rates of progression over time, and may contribute to enhanced patient selection for more intense surveillance programs.
Risk‐scoring system for predicting challenging cases of peroral endoscopic myotomy
Authors: Nakai Tatsuya , Abe Hirofumi , Tanaka Shinwa , Kawara Fumiaki , Toyonaga Takashi , Sakaguchi Hiroya , Ueda Chise , Ikezawa Nobuaki , Tsuda Kazunori , Urakami Satoshi , Kodama Yuzo 
Published: December 2022

ObjectivesPeroral endoscopic myotomy (POEM) is an effective treatment for esophageal motility disorders including achalasia and its variants. However, some surgeons have encountered challenging cases. This study aimed to develop a risk‐scoring system to predict challenging cases of POEM.MethodsConsecutive patients who underwent POEM between April 2015 and March 2020 at our hospital were included in this single‐center retrospective study. Challenging cases of POEM were defined as patients with any of the following: (i) procedure time ≥90 min; (ii) mucosal perforation; (iii) pneumothorax; and (iv) major bleeding. A risk‐scoring system for predicting challenging cases was developed based on multivariate logistic regression and internal validation was performed using the bootstrap method. Clinical usefulness was evaluated using a decision curve analysis.ResultsOf the 467 patients, 59 (12.6%) had challenging POEM. A risk‐scoring system consisted of four variables: duration of symptoms ≥5 years (assigned score, 1 point), antithrombotics use (1 point), manometric diagnosis of achalasia variants (2 points), and dilation grade 3 (2 points). Our scoring system showed satisfactory discrimination (area under the receiver operating characteristic curve, 0.69; 95% confidence interval [CI] 0.61–0.77) and calibration (slope, 0.99; 95% CI 0.65–1.35). The decision curve analysis demonstrated its clinical usefulness.ConclusionsWe established a risk‐scoring system to predict challenging cases of POEM. This scoring system may aid the selection of patients who require treatment from experienced surgeons.
Neurobiological predispositions for musicality: White matter in infancy predicts school‐age music aptitude
Authors: Zuk Jennifer , Vanderauwera Jolijn , Turesky Ted , Yu Xi , Gaab Nadine 
Published: December 2022

AbstractMusical training has long been viewed as a model for experience‐dependent brain plasticity. Reports of musical training‐induced brain plasticity are largely based on cross‐sectional studies comparing musicians to non‐musicians, which cannot address whether musical training itself is sufficient to induce these neurobiological changes or whether pre‐existing neuroarchitecture before training predisposes children to succeed in music. Here, in a longitudinal investigation of children from infancy to school age (n = 25), we find brain structure in infancy that predicts subsequent music aptitude skills at school‐age. Building on prior evidence implicating white matter organization of the corticospinal tract as a neural predisposition for musical training in adults, here we find that structural organization of the right corticospinal tract in infancy is associated with school‐age tonal and rhythmic musical aptitude skills. Moreover, within the corpus callosum, an inter‐hemispheric white matter pathway traditionally linked with musical training, we find that structural organization of this pathway in infancy is associated with subsequent tonal music aptitude. Our findings suggest predispositions prior to the onset of musical training from as early as infancy may serve as a scaffold upon which ongoing musical experience can build.Research Highlights
Structural organization of the right corticospinal tract in infancy is associated with school‐age musical aptitude skills.
Longitudinal associations between the right corticospinal tract in infancy and school‐age rhythmic music aptitude skills remain significant even when controlling for language ability.
Findings support the notion of predispositions for success in music, and suggest that musical predispositions likely build upon a neural structural scaffold established in infancy.
Findings support the working hypothesis that a dynamic interaction between predisposition and experience established in infancy shape the trajectory of long‐term musical development.