bluuebunny/crossref_metadata_2025_split huggingface dataset:
NeoSeq: a new method of genomic sequencing for newborn screening
Authors: Wang Huaiyan , Yang Yuqi , Zhou Lingna , Wang Yu , Long Wei , Yu Bin 
Published: November 2021

Abstract
Objective
To explore the clinical application of NeoSeq in newborn screening.

Methods
Based on the results obtained from traditional newborn screening (NBS) with tandem mass spectrometry (TMS), three cohorts were recruited into the present study: 36 true positive cases (TPC), 60 false-positive cases (FPC), and 100 negative cases. The dried blood spots of the infants were analyzed with NeoSeq, which is based on multiplex PCR amplicon sequencing.

Results
Overall, the sensitivity of NeoSeq was 55.6% (20/36) in the detection of TPC. NeoSeq detected disease-related genes in 20 of 36 TPC infants, while it could not identify these genes in eight children. Five cases (3.1%) with disease risk were additionally found in the FPC and NC cohorts. There was a significant difference in the diagnostic time between the two methods—10 days for NeoSeq vs. 43 days for traditional NBS.

Conclusions
NeoSeq is an economic genomic screening test for newborn screening. It can detect most inborn errors of metabolism, reduce the rate of false positive results, shorten the porting cycles, and reduce the screening cost. However, it is still necessary to further optimize the panel design and add more clinically relevant genomic variants to increase its sensitivity.
Impaired wakefulness and rapid eye movement sleep in dopamine-deficient mice
Authors: Kashiwagi Mitsuaki , Kanuka Mika , Tanaka Kaeko , Fujita Masayo , Nakai Ayaka , Tatsuzawa Chika , Kobayashi Kazuto , Ikeda Kazutaka , Hayashi Yu 
Published: November 2021

AbstractDespite the established roles of the dopaminergic system in promoting arousal, the effects of loss of dopamine on the patterns of sleep and wakefulness remain elusive. Here, we examined the sleep architecture of dopamine-deficient (DD) mice, which were previously developed by global knockout of tyrosine hydroxylase and its specific rescue in noradrenergic and adrenergic neurons. We found that DD mice have reduced time spent in wakefulness. Unexpectedly, DD mice also exhibited a marked reduction in the time spent in rapid eye movement (REM) sleep. The electroencephalogram power spectrum of all vigilance states in DD mice were also affected. These results support the current understanding of the critical roles of the dopaminergic system in maintaining wakefulness and also implicate its previously unknown effects on REM sleep.
Mechanisms of cytokine release syndrome and neurotoxicity of CAR T-cell therapy and associated prevention and management strategies
Authors: Xiao Xinyi , Huang Shengkang , Chen Sifei , Wang Yazhuo , Sun Qihang , Xu Xinjie , Li Yuhua 
Published: November 2021

AbstractChimeric antigen receptor (CAR) T-cell therapy has yielded impressive outcomes and transformed treatment algorithms for hematological malignancies. To date, five CAR T-cell products have been approved by the US Food and Drug Administration (FDA). Nevertheless, some significant toxicities pose great challenges to the development of CAR T-cell therapy, most notably cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Understanding the mechanisms underlying these toxicities and establishing prevention and treatment strategies are important. In this review, we summarize the mechanisms underlying CRS and ICANS and provide potential treatment and prevention strategies.
Analysis of reasons for loss to follow up in a prospective study in Chandigarh, India and impact from telecom changes
Authors: Mathew Joseph L. , Patel Pooja N. , Wagner Abram L. , Suri Vanita , Bharti Bhavneet , Carlson Bradley F. , Boulton Matthew L. 
Published: November 2021

Abstract
Objective
Mobile phones are used in research studies, to enroll and follow-up participants, collect data, and implement mHealth initiatives. We conducted a longitudinal study in a birth cohort, where infants were required to make four scheduled visits by 12 months of age. Families of those failing to attend scheduled follow-up visits, were contacted telephonically to ascertain the reasons, which were categorized as: not interested to continue participating, migrated, phone disconnected due to telecom change, or other reason.

Results
A total of 413 mother-infant dyads were enrolled. The overall attrition was 56%, with majority occurring at the first follow-up visit. This temporally coincided with a telecom service provider announcing strong incentives to switch providers. Attrition monotonically decreased at subsequent visits. The reasons were: moved away (13%), no longer interested (8%), phone disconnected (7%), and multiple other reasons (28%), the majority of whom had unreachable phones. Those who remained in the study and those lost to follow-up were similar on most demographic variables. Among common reasons for attrition in cohort studies, we experienced a new dimension introduced by telecom changes. These findings underscore the need to consider unexpected reasons for attrition in longitudinal studies, and design more robust methods to follow-up participants.
A case of early gastric cancer with a single giant lymph node metastasis
Authors: Yoshikawa Masato , Tamario Misaki , Obatake Masayoshi , Sato Koichi , Yagi Shigehiko , Otani Hiromi , Kito Katsumi 
Published: November 2021

Abstract
Background
Early gastric cancer (EGC) is often associated with lymphatic metastasis, but it is extremely rare to be found as a single giant lymph node. Cancer often becomes more malignant in metastatic lesions than in primary lesions, and retrodifferentiation to the fetal gastrointestinal tract during the metastatic process has been reported in gastric cancer. We report an extremely rare case of EGC with a 13-cm giant lymph node metastasis in which an adenocarcinoma with enteroblastic differentiation and yolk sac tumor-like components was observed.

Case presentation
The case was a 70-year-old man who visited his local doctor with right hypochondrial pain, which was identified by computed tomography (CT) as a giant mass. Upper endoscopy revealed a 30-mm-sized 0-IIc lesion in the greater curvature of the angular incisure and a 15-mm-sized 0-IIa lesion in the anterior wall of the lower body of the gastric body. Endoscopic biopsy revealed tubular adenocarcinoma in both lesions. The gastric lesion and the giant tumor were clinically regarded as independent lesions (gastrointestinal stromal tumor, [GIST], and EGCs), and distal gastrectomy and D1 + dissection were performed to comprehensively treat all lesions. Pathological examination revealed that the giant tumor was tubular adenocarcinoma with an intestinal phenotype and was considered a lymph node metastasis of EGCs. To exclude the possibility of metastasis of adenocarcinoma other than EGCs, postoperative positron emission tomography-computed tomography (PET-CT) and colonoscopy were performed; however, no primary site other than the stomach was found. Metastatic lymph nodes have an increased degree of atypia compared with the primary tumor, and yolk sac tumor-like carcinoma morphology was observed along with α-fetoprotein (AFP) and Spalt-like 4 (SALL4) expression in this case. It was considered that retrodifferentiation to a fetal phenotype occurred during the metastatic process. Liver metastasis occurred 6 months after surgery, and chemotherapy is currently being introduced.

Conclusions
We experienced a case of EGC with a single giant lymph node metastasis. Retrodifferentiation to the fetal gastrointestinal tract during metastasis was speculated to be involved in the formation of giant lymph node metastasis and liver metastasis in this case.
The effect of gender and language proficiency on the metaphor use in the writing of TEFL students
Authors: Fattahi Nazila , Nushi Musa 
Published: November 2021

AbstractThe ubiquitous nature of metaphor in everyday life and its significance in second language learning has triggered plethoric research on the relationship between metaphor and language learning. To contribute to the still growing literature, the current study explore the effect of learner variables, namely gender and proficiency, on metaphor use in TEFL students’ writing. To achieve that objective, 27 intermediate and 23 upper-intermediate Iranian TEFL students were asked to write on an IELTS Writing Task 2 topic. Fifty essays were analyzed for metaphor use through Metaphor Identification Procedure (Pragglejaz Group in Metaphor Symb 22(1):1–39, 2007) and Vehicle Identification Procedure (Cameron in Metaphor in educational discourse, Continuum, London, 2003). The data analyzed through t-test and multiple regression analysis revealed the advantage of upper-intermediate students over intermediate students concerning metaphor use in their writing. Gender, on the other hand, did not play an influential role in the students’ metaphor use. The findings of this research and the implications they might have for the field of English language teaching will be discussed.
Dexmedetomidine versus magnesium sulphate as an adjuvant to local anesthesia in single-injection percutaneous peribulbar anesthesia for cataract extraction
Authors: M. Aya Abuelyossr , Mohammad N. A. , Maghawry Khaled M. , Elderh Maha Sadek , AbdulAziz Mai Mohsen 
Published: November 2021

Abstract
Background
The aim of the study was to evaluate the impact of addition of dexmedetomidine or magnesium sulphate to the standard local anesthetics mixture as a primary objective and to compare between both as a secondary objective utilizing the single-injection percutaneous technique for peribulbar block. In this prospective randomized double-blinded clinical trial (RCT), sixty patients, both sexes, aged 45 to 75, with an ASA of I to III, were scheduled for cataract extraction operation. They were divided into three equal groups; each received a single injection peribulbar block of a mixture of 0.5% bupivacaine (3 ml) + 2 percent lidocaine (3 ml) + 120 IU hyaluronidase + (control group (C): 0.5 ml of normal saline; group D: 50 μg of dexmedetomidine; group M: 50 mg of magnesium sulphate in 0.5 ml) with a total injected volume of 7 ml each. The duration of sensory, motor block, need for supplementary doses, hemodynamics, and satisfaction of patients and surgeons were assessed.

Results
For the primary outcome, both the dexmedetomidine and magnesium groups revealed statistically significant differences from the control group with shorter onsets of sensory block and lid akinesia (p value< 0.001 for both), shorter onset of globe akinesia for dexmedetomidine (p value<0.001) and for magnesium sulphate (p value=0.022), prolonged duration of lid and globe akinesia and sensory block (p value<0.001), better patient satisfaction (p value=0.044) but insignificant difference regarding surgeons’ satisfaction (p value= 0.117) and a less frequent, but statistically insignificant need for supplementary injection (p value=0.075). The demographic and clinical hemodynamics and oxygen saturation parameters were comparable between the three groups. For the secondary outcome, dexmedetomidine was superior to magnesium sulphate regarding onset of globe and lid akinesia (p value= 0.047 and 0.003, respectively), and durations of globe akinesia and sensory block (p value= 0.02 and 0.016, respectively). No complications related to the drugs or procedure were recorded.

Conclusions
When compared to 50 mg magnesium sulphate, dexmedetomidine at a dose of 50 μg is a superior adjunct to local anesthetic combination in peribulbar block for cataract procedures in terms of start and duration of peribulbar block.
Multistage closure of a congenital extrahepatic portosystemic shunt
Authors: Facas João , Cruz Manuel , Costa João Filipe , Agostinho Alfredo , Donato Paulo 
Published: November 2021

Abstract
Background
Congenital extrahepatic portosystemic shunts (CEPS) are rare shunts connecting the extrahepatic portal system with the inferior vena cava. Shunt dimensions and the risk of portal hypertension determines the closure strategy. Endovascular treatment is indicated for single stage occlusion of longer length shunts, whereas the remaining shunt types are preferentially surgically occluded. Herein we describe the technical details of a novel endovascular treatment for short length CEPS.

Case presentation
A 15-years-old male with a short length CEPS complicated with multinodular liver disease was submitted to a multistage closure, as indicated by the high portal pressure values during shunt balloon occlusion venography. Initially a transjugular intrahepatic portosystemic shunt (TIPS) was created and the CEPS occluded with an atrial septal defect occluder. In a second procedure the TIPS was embolized with a flow reductor stent and an amplatzer vascular plug II. At a 1 year follow up the liver nodules size reduced, the patient remains asymptomatic, and the shunt adequately closed.

Conclusion
This paper outlines the potential use of a TIPS and an atrial septal defect occluder combination in complex CEPS, supporting its usage as an alternative to the standard surgical treatment.
Level of Evidence: Level 4, Case report.
Effect of caffeine on delayed-onset muscle soreness: a meta-analysis of RCT
Authors: Muljadi Janisa Andrea , Kaewphongsri Patsorn , Chaijenkij Kornkit , Kongtharvonskul Jatupon 
Published: November 2021

AbstractBackgroundThere are multiple strategies that have been suggested to attenuate delayed-onset muscle soreness (DOMS). Caffeine has been shown to assist with blocking pain associated with DOMS. However, currently there is still controversy over the effects of caffeine use.Main bodyWe conducted a meta-analysis to compare pain associated with muscle soreness by both the VAS and indirect markers by CK of caffeine and placebo after exercise. The meta-analysis was carried out in accordance with the PRISMA guidelines. Relevant studies from Medline and Scopus published up to May 20, 2021, were included, which resulted in a total of 477 and 132 studies being retrieved from Scopus and Medline, respectively. Seven studies met the inclusion criteria, and in these, there were 68 persons in the caffeine group and 74 persons in the placebo group. A visual analog score of muscle soreness was recorded pre-exercise, immediately post-exercise, and at one to four days post-exercise; the scores at these time points in the caffeine group as compared to those in the placebo group progressed from 0.00 (95% CI − 0.51, 0.50) to − 0.20 (− 1.09, 0.69), − 0.92 (− 2.20, 0.36), − 1.02 (− 1.86, − 0.19), 0.00 (− 0.36, 0.36), and 0.18 (− 0.56, 0.92), respectively. No statistically significant differences were noted for CK between the two groups at 24 h post-exercise.Short conclusionOur meta-analysis results indicate that caffeine supplements reduce delayed-onset muscle soreness when compared to a placebo 48 h after exercise. However, at 24 h post-exercise, caffeine can reduce DOMS only in people who worked on resistant exercise. The CK used in this meta-analysis did not show any differences.Trial registration: PROSPERO CRD42021260248.Level of evidenceI.
Milk microbiome in dairy cattle and the challenges of low microbial biomass and exogenous contamination
Authors: Pollock Jolinda , Salter Susannah J. , Nixon Rebecca , Hutchings Michael R. 
Published: November 2021

Abstract
Background
The blanket usage of antimicrobials at the end of lactation (or “drying off”) in dairy cattle is under increasing scrutiny due to concerns about antimicrobial resistance. To lower antimicrobial usage in dairy farming, farmers are now encouraged to use “selective dry cow therapy” whereby only cows viewed as at high risk of mastitis are administered antimicrobial agents. It is important to gain a better understanding of how this practice affects the udder-associated microbiota and the potential knock-on effects on antimicrobial-resistant bacterial populations circulating on the farm. However, there are challenges associated with studying low biomass environments such as milk, due to known contamination effects on microbiome datasets. Here, we obtained milk samples from cattle at drying off and at calving to measure potential shifts in bacterial load and microbiota composition, with a critical assessment of contamination effects.

Results
Several samples had no detectable 16S rRNA gene copies and crucially, exogenous contamination was detected in the initial microbiome dataset. The affected samples were removed from the final microbiome analysis, which compromised the experimental design and statistical analysis. There was no significant difference in bacterial load between treatments (P > 0.05), but load was lower at calving than at drying off (P = 0.039). Escherichia coli counts by both sequence and culture data increased significantly in the presence of reduced bacterial load and a decreasing trend of microbiome richness and diversity. The milk samples revealed diverse microbiomes not reflecting a typical infection profile and were largely comprised of gut- and skin-associated taxa, with the former decreasing somewhat after prolonged sealing of the teats.

Conclusions
The drying off period had a key influence on microbiota composition and bacterial load, which appeared to be independent of antimicrobial usage. The interactions between drying off treatment protocol and milk microbiome dynamics are clearly complex, and our evaluations of these interactions were restricted by low biomass samples and contamination effects. Therefore, our analysis will inform the design of future studies to establish whether different selection protocols could be implemented to further minimise antimicrobial usage.
Thoracic surgery in the COVID-19 era: an Italian university hospital experience
Authors: Taje Riccardo , Elia Stefano , Cristino Benedetto , Tacconi Federico , Natali Gianluca , Ambrogi Vincenzo , Pompeo Eugenio 
Published: November 2021

Abstract
Background
Aims of this study were to assess the results of anti-COVID19 measures applied to maintain thoracic surgery activity at an Italian University institution through a 12-month period and to assess the results as compared with an equivalent non-pandemic time span.

Methods
Data and results of 646 patients operated on at the department of Thoracic Surgery of the Tor Vergata University Policlinic in Rome between February 2019 and March 2021 were retrospectively analyzed. Patients were divided in 2 groups: one operated on during the COVID-19 pandemic (pandemic group) and another during the previous non-pandemic 12 months (non-pandemic group). Primary outcome measure was COVID-19 infection-free rate.

Results
Three patients developed mild COVID-19 infection early after surgery resulting in an estimated COVID-19 infection-free rate of 98%. At intergroup comparisons (non-pandemic vs. pandemic group), a greater number of patients was operated before the pandemic (352 vs. 294, p = 0.0013). In addition, a significant greater thoracoscopy/thoracotomy procedures rate was found in the pandemic group (97/151 vs. 82/81, p = 0.02) and the total number of chest drainages (104 vs. 131, p = 0.0001) was higher in the same group. At surgery, tumor size was larger (19.5 ± 13 vs. 28.2 ± 21; p < 0.001) and T3-T4/T1-T2 ratio was higher (16/97 vs. 30/56; p < 0.001) during the pandemic with no difference in mortality and morbidity. In addition, the number of patients lost before treatment was higher in the pandemic group (8 vs. 15; p = 0.01). Finally, in 7 patients admitted for COVID-19 pneumonia, incidental lung (N = 5) or mediastinal (N = 2) tumors were discovered at the chest computed tomography.

Conclusions
Estimated COVID-19 infection free rate was 98% in the COVID-19 pandemic group; there were less surgical procedures, and operated lung tumors had larger size and more advanced stages than in the non-pandemic group. Nonetheless, hospital stay was reduced with comparable mortality and morbidity. Our study results may help implement efficacy of the everyday surgical care.
Random-PE: an efficient integration of random sequences into mammalian genome by prime editing
Authors: Jiao Yaoge , Zhou Lifang , Tao Rui , Wang Yanhong , Hu Yun , Jiang Lurong , Li Li , Yao Shaohua 
Published: November 2021

AbstractPrime editing (PE) enables efficiently targeted introduction of multiple types of small-sized genetic change without requiring double-strand breaks or donor templates. Here we designed a simple strategy to introduce random DNA sequences into targeted genomic loci by prime editing, which we named random prime editing (Random-PE). In our strategy, the prime editing guide RNA (pegRNA) was engineered to harbor random sequences between the primer binding sequence (PBS) and homologous arm (HA) of the reverse transcriptase templates. With these pegRNAs, we achieved efficient targeted insertion or substitution of random sequences with different lengths, ranging from 5 to 10, in mammalian cells. Importantly, the diversity of inserted sequences is well preserved. By fine-tuning the design of random sequences, we were able to make simultaneously insertions or substitutions of random sequences in multiple sites, allowing in situ evolution of multiple positions in a given protein. Therefore, these results provide a framework for targeted integration of random sequences into genomes, which can be redirected for manifold applications, such as in situ protospacer adjacent motif (PAM) library construction, enhancer screening, and DNA barcoding.
Approach to the Patient With Pseudoacromegaly
Authors: Marques Pedro , Korbonits Márta 
Published: November 2021

AbstractPseudoacromegaly encompasses a heterogeneous group of conditions in which patients have clinical features of acromegaly or gigantism, but no excess of GH or IGF-1. Acromegaloid physical features or accelerated growth in a patient may prompt referral to endocrinologists. Because pseudoacromegaly conditions are rare and heterogeneous, often with overlapping clinical features, the underlying diagnosis may be challenging to establish. As many of these have a genetic origin, such as pachydermoperiostosis, Sotos syndrome, Weaver syndrome, or Cantú syndrome, collaboration is key with clinical geneticists in the diagnosis of these patients. Although rare, awareness of these uncommon conditions and their characteristic features will help their timely recognition.