bluuebunny/crossref_metadata_2025 huggingface dataset:
Hebraism
Authors: Grosby Steven
Published: April 2021

This chapter examines Hebraism as the ‘third culture’, distinct from Greek and Roman Christianity, as a kind of Jewish Christianity. Hebraism, as a current of intellectual history, is expressed in the work of the Christian Hebraists of early modern Europe, the quintessential example being John Selden. Hebraism’s focus on life in this world led to the problems of how life should be organized through law, the territorialization of tradition, and the paradoxical national monotheism of the ‘new Israel’. A different interpretation of the Old Testament emerged, influencing the relation between the Old and New Testaments. The theological, political, legal, and social characteristics of Hebraic culture are clarified.
Neural Basis of Speech-Gesture Mismatch Detection in Schizophrenia Spectrum Disorders
Authors: Choudhury Momoko , Steines Miriam , Nagels Arne , Riedl Lydia , Kircher Tilo , Straube Benjamin
Published: April 2021

Patients with schizophrenia spectrum disorders (SSD) exhibit an aberrant perception and comprehension of abstract speech-gesture combinations associated with dysfunctional activation of the left inferior frontal gyrus (IFG). Recently, a significant deficit of speech-gesture mismatch detection was identified in SSD, but the underlying neural mechanisms have not yet been examined. A novel mismatch-detection fMRI paradigm was implemented manipulating speech-gesture abstractness (abstract/concrete) and relatedness (related/unrelated). During fMRI data acquisition, 42 SSD patients (schizophrenia, schizoaffective disorder, or other non-organic psychotic disorder [ICD-10: F20, F25, F28; DSM-IV: 295.X]) and 36 healthy controls were presented with short video clips of an actor reciting abstract or concrete sentences accompanied by either a semantically related or unrelated gesture. Participants indicated via button press whether they perceived each gesture as matching the speech content or not. Speech-gesture mismatch detection performance was significantly impaired in patients compared to controls. fMRI data analysis revealed that patients showed lower activation in bilateral frontal areas, including the IFG for all abstract > concrete speech-gesture pairs. In addition, they exhibited reduced engagement of the right supplementary motor area (SMA) and bilateral anterior cingulate cortices (ACC) for unrelated > related stimuli. We provide first evidence that impaired speech-gesture mismatch detection in SSD could be the result of dysfunctional activation of the SMA and ACC. Failure to activate the left IFG disrupts the integration of abstract speech-gesture combinations in particular. Future investigations should focus on brain stimulation of the SMA, ACC, and the IFG to improve communication and social functioning in SSD.
Three overlooked key functional classes for building up minimal synthetic cells
Authors: Danchin Antoine
Published: April 2021

Assembly of minimal genomes revealed many genes encoding unknown functions. Three overlooked functional categories account for some of them. Cells are prone to make errors and age. As a first key function, discrimination between proper and changed entities is indispensable. Discrimination requires management of information, an authentic, yet abstract, currency of reality. For example proteins age, sometimes very fast. The cell must identify, then get rid of old proteins without destroying young ones. Implementing discrimination in cells leads to the second set of functions, usually ignored. Being abstract, information must nevertheless be embodied into material entities, with unavoidable idiosyncratic properties. This brings about novel unmet needs. Hence, the buildup of cells elicits specific but awkward material implementations, ‘kludges’ that become essential under particular settings, while difficult to identify. Finally, a third functional category characterizes the need for growth, with metabolic implementations allowing the cell to put together the growth of its cytoplasm, membranes, and genome, spanning different spatial dimensions. Solving this metabolic quandary, critical for engineering novel synthetic biology chassis, uncovered an unexpected role for CTP synthetase as the coordinator of nonhomothetic growth. Because a significant number of SynBio constructs aim at creating cell factories we expect that they will be attacked by viruses (it is not by chance that the function of the CRISPR system was identified in industrial settings). Substantiating the role of CTP, natural selection has dealt with this hurdle via synthesis of the antimetabolite 3′-deoxy-3′,4′-didehydro-CTP, recruited for antiviral immunity in all domains of life.
Transmission dynamics of SARS-CoV-2 within-host diversity in two major hospital outbreaks in South Africa
Authors: San James E , Ngcapu Sinaye , Kanzi Aquillah M , Tegally Houriiyah , Fonseca Vagner , Giandhari Jennifer , Wilkinson Eduan , Nelson Chase W , Smidt Werner , Kiran Anmol M , Chimukangara Benjamin , Pillay Sureshnee , Singh Lavanya , Fish Maryam , Gazy Inbal , Martin Darren P , Khanyile Khulekani , Lessells Richard , de Oliveira Tulio
Published: April 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes acute, highly transmissible respiratory infection in humans and a wide range of animal species. Its rapid global spread has resulted in a major public health emergency, necessitating commensurately rapid research to improve control strategies. In particular, the ability to effectively retrace transmission chains in outbreaks remains a major challenge, partly due to our limited understanding of the virus’ underlying evolutionary dynamics within and between hosts. We used high-throughput sequencing whole-genome data coupled with bottleneck analysis to retrace the pathways of viral transmission in two nosocomial outbreaks that were previously characterised by epidemiological and phylogenetic methods. Additionally, we assessed the mutational landscape, selection pressures, and diversity at the within-host level for both outbreaks. Our findings show evidence of within-host selection and transmission of variants between samples. Both bottleneck and diversity analyses highlight within-host and consensus-level variants shared by putative source-recipient pairs in both outbreaks, suggesting that certain within-host variants in these outbreaks may have been transmitted upon infection rather than arising de novo independently within multiple hosts. Overall, our findings demonstrate the utility of combining within-host diversity and bottleneck estimations for elucidating transmission events in SARS-CoV-2 outbreaks, provide insight into the maintenance of viral genetic diversity, provide a list of candidate targets of positive selection for further investigation, and demonstrate that within-host variants can be transferred between patients. Together these results will help in developing strategies to understand the nature of transmission events and curtail the spread of SARS-CoV-2.
Streamlining Follicular Monitoring During Controlled Ovarian Stimulation: A Data-Driven Approach to Efficient IVF Care in the New Era of Social Distancing
Authors: Robertson I. , Chmiel F. P. , Cheong Y.
Published: April 2021

(Abstracted from Hum Reprod 2021;36(1):99–106)

During controlled ovarian stimulation (COS) as part of in vitro fertilization (IVF), routine monitoring using transvaginal ultrasound is indicated in order to identify the most appropriate time to trigger final follicular maturation and to identify signs of overresponse. Evidence regarding the ideal protocol and frequency of monitoring COS patients in order to maximize live birth rate and minimize morbidity has been inconclusive.
Large Individual Bilateral Differences in Tibial Torsion Impact Accurate Contralateral Templating and the Evaluation of Rotational Malalignment
Authors: Gallo Matthew C. , Tucker Douglass W. , Reddy Akhil , Pannell William C. , Heckmann Nathanael , Marecek Geoffrey S.
Published: April 2021

Objective:

To determine individual bilateral differences (IBDs) in tibial torsion in a diverse population.

Methods:

Computed tomography scans of uninjured bilateral tibiae were used to determine tibial torsion and IBDs in torsion using 4 measurement methods. Age, sex, and self-identified race/ethnicity were also recorded for each subject. Mean tibial torsion and IBDs in torsion were compared in the overall cohort and when stratified by sex and race/ethnicity. Simple and multiple linear regression models were used to correlate demographic variables with tibial torsion and IBDs in torsion.

Results:

One hundred ninety-five patients were evaluated. The mean tibial torsion was 27.5 ± 8.3 degrees (range −3 to 47.5 degrees). The mean IBD in torsion was 5.3 ± 4.0 degrees (range 0–23.5 degrees, P < 0.001). 12.3% of patients had IBDs in torsion of ≥10 degrees. In the regression analysis, patients who identified as White had greater average torsion by 4.4 degrees compared with Hispanic/Latinx patients (P = 0.001), whereas age and sex were not significantly associated with absolute torsion. Demographics were not associated with significant differences in IBDs in torsion.

Conclusions:

Tibial torsion varies considerably and individual side-to-side differences are common. Race/ethnicity was associated with differences in the magnitude of tibial torsion, but no factors were associated with bilateral differences in torsion. The results of this study may be clinically significant in the context of using the uninjured contralateral limb to help establish rotational alignment during medullary nail stabilization of diaphyseal tibia fractures. In addition, these findings should be considered in the evaluation of tibia rotational malalignment.

Level of Evidence:

Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Nasal Embryonal Rhabdomyosarcoma in the Pediatric Population: Literature Review and Report of Midline Presentation
Authors: Larson Jordan H. , Rutledge Rachel , Hunnell Laura , Choi Daniel K. , Kellogg Robert G. , Naran Sanjay
Published: April 2021

Background:

Congenital midline nasal masses are rare anomalies and are typically benign nasal dermoid sinus cysts (NDSCs). Rhabdomyosarcomas (RMSs) are even less common, and only a fraction affect sites like the external nose, nasal cavity, nasopharynx, and paranasal sinuses. We review the clinical presentation and treatment of nasal, nasopharyngeal, and paranasal RMSs and report the first documented midline presentation.

Methods:

We queried PubMed for articles with titles containing the terms rhabdomyosarcoma or sarcoma botryoides and nose, nasal, paranasal, sinonasal, nasopharynx, or nasopharyngeal. We then searched the references of each included article using the same parameters and continued this process iteratively until no new articles were found.

Results:

The paranasal sinuses were the most commonly affected site, followed by the nasopharynx, nasal cavity, and external nose. Two patients presented with involvement of the external nose, but each presented with involvement of the right ala rather than a midline mass. The rates of intracranial extension and/or skull base involvement were comparable to those of NDSCs. The alveolar subtype was most common, followed by the embryonal subtype.

Conclusions:

Most midline nasal masses are benign; however, we report the first documented presentation of an RMS as a midline nasal mass. Accordingly, RMS should be included in the differential diagnosis of midline nasal masses in the pediatric population. Surgery for midline nasal masses is sometimes delayed due to the risks of interfering with developing structures and early anesthesia. However, early surgical treatment should be considered given this new differential and its predilection for early metastasis.
Role of Regulatory Cells in Immune Tolerance Induction in Hemophilia A
Authors: Schep Sarah J. , Schutgens Roger E. G. , Fischer Kathelijn , Voorberg Jan , Boes Marianne
Published: April 2021

The main complication of hemophilia A treatment is the development of neutralizing antibodies (inhibitors) against factor VIII (FVIII). Immune tolerance induction (ITI) is the prescribed treatment for inhibitor eradication, although its working mechanism remains unresolved. To clarify this mechanism, we compared blood samples of hemophilia A patients with and without inhibitors for presence of immunoregulatory cells and markers, including regulatory B-cells (Bregs), regulatory T-cells (Tregs), myeloid-derived suppressor cells (MDSCs), and expression of regulatory markers on T-cells (programmed cell death protein 1 [PD1], inducable T-cell costimulator, cytotoxic T-lymphocyte-associated protein 4 [CTLA4]), by use of flow cytometry. By cross-sectional analysis inhibitor patients (N = 20) were compared with inhibitor-negative (N = 28) and ex-inhibitor (N = 17) patients. In another longitudinal study, changes in immunoregulatory parameters were evaluated during ITI (N = 12) and compared with inhibitor-negative hemophilia A patients (N = 36). The frequency of Bregs, but not of Tregs nor MDSCs, was significantly reduced in inhibitor patients (3.2%) compared with inhibitor-negative (5.9%) and ex-inhibitor patients (8.9%; P < 0.01). CTLA4 expression on T-cells was also reduced (mean fluorescence intensity 133 in inhibitor versus 537 in inhibitor-negative patients; P < 0.01). Fittingly, in patients followed during ITI, inhibitor eradication associated with increased Bregs, increased Tregs, and increased expression of CTLA4 and PD1 on CD4+ T-cells. In conclusion, inhibitor patients express significantly lower frequency of Bregs and Tregs marker expression, which are restored by successful ITI. Our findings suggest that an existing anti-FVIII immune response is associated with deficits in peripheral tolerance mechanisms and that Bregs and changes in immunoregulatory properties of CD4+ T-cells likely contribute to ITI in hemophilia A patients with inhibitors.
Hydraulic- and Microprocessor-Controlled Ankle-Foot Prostheses for Limited Community Ambulators with Unilateral Transtibial Amputation: Pilot Study
Authors: Kaluf Brian , Cox Courtney , Shoemaker Eric
Published: April 2021

Introduction

In the United States, access to microprocessor-controlled prosthetic ankles is limited to patients with lower-limb loss classified as unlimited community ambulators or greater. However, the potential benefits of these devices have not been evaluated among patients classified as household or limited community ambulators. This study examined the benefit of hydraulic- and microprocessor-controlled prosthetic ankles for patients classified as limited community ambulators.

Materials and Methods

Four different treatment configurations were evaluated using a randomized crossover study design. These four configurations included the participant's current flexible keel (FK) prosthetic foot, an energy-storage-and-return foot (ESAR), a hydraulic ankle (HA), and a microprocessor ankle (MPA). After a 2-week accommodation period, both patient-reported and performance-based outcome measures were recorded for each ankle foot system. A StepWatch activity monitor and two-dimensional video motion analysis were also used to evaluate each system.

Results

A single participant meeting the inclusion criteria was recruited. The patient-reported mobility and socket fit instruments were greatest with the HA system. When assessed on slopes and stairs, the MPA demonstrated benefits on hill ascent and stair descent. In considering the walking speed and perceived exertion jointly, the HA system allowed similar walking speed but lower exertion compared with fixed-ankle systems. The patient-reported low back pain and balance confidence instruments did not provide useful data for interpretation. Two-dimensional video motion analysis showed that the HA and MPA contributed to improved ankle and knee postures when ascending and descending a slope. The step activity data showed the greatest activity with the HA.

Discussion

The results from the outcome measures showed a varying level of benefit across all four of the treatment configurations. Both the HA and MPA had favorable scores in varying performance-based outcome measures, but the HA scored the most favorable in a majority of the patient-reported outcome measures.

Conclusion

The results show varying benefits of the microprocessor- and hydraulic-controlled prosthetic components over fixed-ankle ESAR and FK feet, based on both performance-based and patient-reported outcome measures. Further studies are needed to fully evaluate these benefits in larger sample sizes.
Comparison of gait recovery patterns according to the paralyzed side in stroke patients
Authors: Kim Cheol-Hyun , Chu Hongmin , Kang Geon-Hui , Kim Kwang-Ho , Lee Young-Ung , Lim Hyeon-Seo , Sung Kang-Keyng , Lee Sangkwan
Published: April 2021

Gait rehabilitations have been abundantly performed for post-stroke patients, because gait is the most important factor for the return of post-stroke patients to daily life. However, conventional uniform gait rehabilitations tend to be tedious and reduce motivation. The aim of this study was to contribute to the development of personalized rehabilitation of gait by identifying differences in gait recovery pattern according to the paralyzed side of post-stroke patients.

The gait analysis was performed on stroke patients who are right-handed and can walk independently. We retrospectively analyzed the results of pelvic movements and displacement of center of pressure (COP) during gait using corresponding equipments. To show the difference of gait recovery pattern according to the paralyzed side, we divided subjects into two groups, right (n = 19) and left (n = 20) hemiparesis group. The measured variables were as follows: tilt, obliquity, and rotation symmetries of pelvis; area, velocity, and lateral symmetry of COP.

First, in the left hemiparesis group, obliquity (P < .01) and rotation (P < .01) symmetries of the movement of the pelvis were significantly improved in the follow-up compared to the initial gait analysis. In the right hemiparesis group, tilt (P < .001), obliquity (P < .001), and rotation (P < .05) symmetries were significantly improved in the follow-up compared to the initial gait analysis. Second, COP area and COP velocity values in the follow-up were significantly smaller than those in the initial gait analysis in the left (P < .001, P < .05) and right (P < .001, P < .01) hemiparesis groups. The positive value of lateral symmetry increased, although not a significant difference statistically, as walking ability improved in both groups. In the correlation analysis among variables obtained using Treadmill, there were significant positive linear relationships between the lateral symmetry and the COP area (P < .05), and between the COP velocity and the lateral symmetry (P < .001) of the follow-up gait analysis in the right hemiparesis group.

It was confirmed that the gait recovery pattern differs according to the paralyzed side of post-stroke patients and the role of the intact side, such as moving the COP to the intact side, is important for the improvement of gait function in both groups.

This study was registered with the Clinical Research Information Service (CRIS) of the Korea National Institute of Health (NIH), Republic of Korea (KCT0002984) and was approved by the Institutional Review Board (IRB) of the WKUGH (WKIRB [2018-25], November 28, 2018).
Varied clinical significance of ATP-binding cassette C sub-family members for lung adenocarcinoma
Authors: Zhang Linbo , Huang Ping , Huang Chunxia , Jiang Lingmei , Lu Zhijie , Wang Peng
Published: April 2021

Lung adenocarcinoma (LUAD) is a lethal malignancy worldwide and a major public health concern. We explored the potential clinical significance for LUAD of ATP-binding cassette (ABC), sub-family C, consisting of ABCC1–6, 8–12, and cystic fibrosis transmembrane conductance regulator (CFTR).

Five hundred LUAD patients from The Cancer Genome Atlas database were used for analysis, including differential expression and diagnostic and prognostic significance. Oncomine and MERAV databases were used to validate differential expression and diagnostic significance. A risk score model was constructed using prognosis-related ABCC members. Prognosis-related genes were further explored to correlate their expression with tumor stage progression. Interaction networks, including biological processes and metabolic pathways, were constructed using Cytoscape software and STRING website.

ABCC1–3 consistently showed high expression in tumor tissues (all P ≤ 0.05). Most datasets indicated that ABCC5, 10, and 11 were highly expressed in tumor tissues whereas ABCC6, 9, and CFTR were highly expressed in nontumor tissues (all P ≤ 0.05). Diagnostic significance of ABCC3 and ABCC5 was consistently assessed and validated in three datasets (all area under the curve > 0.700) whereas ABCC6, 8, 10, 11, and CFTR were assessed in The Cancer Genome Atlas dataset and validated in one dataset (all area under the curve > 0.700). Prognostic analysis indicated that ABCC2, 6, and 8 mRNA expression was associated with survival of LUAD (all adjusted P ≤ .037). The risk score model constructed using ABCC2, 6, and 8 suggested prognostic significance for survival predictions. ABCC2 expression was associated with tumor stage, whereas ABCC6 and 8 were not. Interaction networks indicated that they were involved in establishment of localization, ion transport, plasma membrane, apical plasma membrane, adenylyl nucleotide binding, ABC transporters, ABC transporter disorders, ABC-family-protein-mediated transport, and bile secretion.

Differentially expressed ABCC2 and ABCC5 might be diagnostic whereas ABCC2, 6, and 8 may be prognostic biomarkers for LUAD, possibly through ABC-family-mediated transporter disorders.
Spectrum of imaging findings of papillary breast disease
Authors: Fadzli Farhana , Rahmat Kartini , Ramli Marlina Tanty , Rozalli Faizatul Izza , Hooi Teoh Kean , Fadzli Ahmad Nazran , Hoong See Mee , Ramli Norlisah Mohd , Taib Nur Aishah Mohd
Published: April 2021

To evaluate the clinical and imaging findings of papillary breast neoplasm and review the pathologic correlation at a tertiary center.

Retrospective study of patients diagnosed with benign and malignant papillary lesions between 2008 to 2018. 147 patients were identified with histology diagnosis of papillary lesions. The clinical, imaging, and pathological characteristics were reviewed.

Patient cohort included 147 women diagnosed with papillary lesions (mean age at diagnosis 53.8 years) and were divided into 3 histology groups (benign, atypical, and malignant). Common clinical presentations were breast lump (n = 60) and nipple discharge (n = 29), 48 patients were asymptomatic.

Only 37 were detected as a mass lesion on mammogram. The presence of mass lesion on mammogram was the most common feature in all 3 papillary lesion groups, and with the presence of asymmetric density, were the 2 mammographic features significantly associated (P < .05) with malignancy.

All lesions were detected on ultrasound. The most common sonographic features for all 3 groups were the presence of a mass and irregular shape. Among all the sonographic features assessed, larger size, presence of vascularity and absence of dilated ducts were significantly associated (P < .05) with malignancy.

Feature pattern recognition of the variety of benign, atypical and malignant papillary neoplasm on ultrasound and mammogram, with emphasis on size, presence of vascularity and dilated ducts on ultrasound and presence of mass, and architectural distortion on mammogram, is important in the assessment of patients with suspected ductal lesions to facilitate optimal treatment and surgical care.
Cycling or swap biologics and small molecules in psoriatic arthritis
Authors: Ariani Alarico , Santilli Daniele , Mozzani Flavio , Lumetti Federica , Lucchini Gianluca , Di Donato Eleonora , Giordano Salvatore , Riva Michele , Becciolini Andrea
Published: April 2021

During the last years there has been an increasing availability of drugs (biologics and small molecules) with different mechanisms of action (MoA) in psoriatic arthritis (PsA). New issues about treatment strategies have arisen. The main aim of this study is to verify if there is a difference in terms of clinical efficacy (i.e. retention rate) between cycling (i.e. treating patients with the same MoA after the failure of the previous one) or swap (i.e choosing drugs with a MoA different from the failed previous one) strategies in PsA.

In this mono-centric medical records review study, PsA patients treated with biologics, apremilast or tofacitinib were enrolled. Every prescription was clustered in three groups: cycling (CG), swap (SG) or first line group (1LG). Kaplan-Meier analysis and Cox test estimated and compared drugs’ retention rate in CG, SG and 1LG. P < .05 was considered statistically significant.

One hundred eighty-three PsA patients were enrolled (9967 patient-months). In CG and 1LG the more prescribed drugs were tumor necrosis factor inhibitor (respectively 99% and 89%), in SG interleukin 17 inhibitor (60%). There were no differences in terms of sex, age, disease duration, and retention rate between CG and SG. The 18-months retention rate of 1LG, SG and CG was 77%, 60%, and 51% respectively. The CG retention rate was lower than in 1LG (P = .03).

The findings of this study suggest that in PsA the swap strategy gives no remarkable advantage compared to cycling. However, patients undergoing swap strategy may experience the same failure rate observed in naives.
A successful case of varix of the left gastroepiploic vein preoperatively diagnosed by 3D-CT angiography and resected by laparoscopy
Authors: Matsuo Kentaro , Lee Sang-Woong , Tanaka Ryo , Imai Yoshiro , Honda Kotaro , Yamamoto Kazuhiro , Uchiyama Kazuhisa
Published: April 2021

Introduction:

Gastric varices can be present in up to 20% of patients with portal hypertension. However, a varix of the left gastroepiploic vein (LGV) is extremely rare. Surgery is required if bleeding occurs; thus, precise diagnosis is crucial. We present a successful case of preoperative diagnosis intraabdominal varix of the LGV using three-dimensional-computed tomography angiography (3D-CTA) followed by laparoscopic resection. This is the first report of a case with variant LGV. Our study demonstrates the efficacies of 3D-CTA and laparoscopic surgery for the diagnosis and safe resection of the intraabdominal varix, respectively.

Patient concerns:

A 74-year-old woman was referred to our department with a tumor in the abdominal cavity. On physical examination, no lumps were palpable in the upper abdomen.

Diagnosis:

The enhanced CT was revealed that the tumor was not enhanced in the early phase, but in the equilibrium phase. Moreover, 3D-CTA clearly revealed that the tumor was being supplied by the LGV. Thus, it was diagnosed as a variant of the LGV.

Interventions:

Surgical resection was performed laparoscopically as per the guidance of preoperative 3D-CTA findings. During surgery, a dark tumor was found along the gastroepiploic vessels, supplied by the LGV. The tumor was resected safely based on the preoperative information.

Outcomes:

Histopathological examination of the tumor showed accumulation of various vessels, but no malignant cells. Therefore, we made a final diagnosis of the tumor as an LGV varix. For follow-up, an annual CT examination was performed and after 3 years postoperation, no recurrence was observed.

Conclusions:

In the present case, we have achieved a successful preoperative diagnosis using 3D-CTA, and resection was safely accomplished using laparoscopy guided by preoperative anatomical information. This is the first report of an LGV variant. Appropriate management is crucial because bleeding is a catastrophic event. Therefore, imaging procedures such as 3D-CTA for diagnosis, followed by safe resection by laparoscopic surgery, are effective tools for the treatment of epiploic vein varices.
Effectiveness and safety of traditional Chinese medicine in the treatment of senile hypotension
Authors: Chen Zhijun , Zhu Siyuan , Liu Meihua , Tang Genhua , Zhong Zhiying , Lu LunBin
Published: April 2021

Background:

Senile hypotension refers to those whose blood pressure (BP) is lower than 90/60 mm Hg. The consequences can not only cause insufficient cardio-cerebral perfusion, but severe cases may also cause angina pectoris and stroke. At present, Western medicine has no ideal therapeutic drugs for senile hypotension. The aim of this systematic review is to assess the effectiveness and safety of traditional Chinese medicine (TCM) therapy for senile hypotension.

Methods:

Two reviewers will electronically search the following databases: the Cochrane Central Register of Controlled Trials; PubMed; EMBASE; China National Knowledge Infrastructure; Chinese Biomedical Literature Database; Chinese Scientific Journal Database (VIP database); and Wan-Fang Database from the inception, without restriction of publication status and languages. Additional searching including researches in progress, the reference lists and the citation lists of identified publications. Study selection, data extraction, and assessment of study quality will be performed independently by 2 reviewers. If it is appropriate for a meta-analysis, RevMan 5.4 statistical software will be used; otherwise, a descriptive analysis will be conducted. Data will be synthesized by either the fixed-effects or random-effects model according to a heterogeneity test. The results will be presented as risk ratio (RR) with 95% confidence intervals (CIs) for dichotomous data and weight mean difference (WMD) or standard mean difference 95% CIs for continuous data.

Results:

This study will provide a comprehensive review of the available evidence for the treatment of TCM with senile hypotension.

Conclusions:

The conclusions of our study will provide an evidence to judge whether TCM is an effective and safe intervention for patients with senile hypotension.

Ethics and dissemination:

This systematic review will be disseminated in a peer-reviewed journal or presented at relevant conferences. It is not necessary for a formal ethical approval because the data are not individualized.

Trial registration number:

INPLASY2020110091.
In silico screening using bulk and single-cell RNA-seq data identifies RIMS2 as a prognostic marker in basal-like breast cancer
Authors: Zhang Lingyun , Liu Zheng , Zhu Jingqiang
Published: April 2021

Single-cell RNA-seq has become a powerful tool to understand tumor cell heterogenicity. This study tried to screen prognosis-related genes in basal-like breast tumors and evaluate their correlations with cellular states at the single-cell level.

Bulk RNA-seq data of basal-like tumor cases from The Cancer Genome Atlas-Breast Cancer (TCGA-BRCA) and single-cell RNA-seq from GSE75688 were retrospectively reviewed. Kaplan–Meier survival curves, univariate and multivariate analysis based on Cox regression model were conducted for survival analysis. Gene set enrichment analysis (GSEA) and single-cell cellular functional state analysis were performed.

Twenty thousand five hundred thirty genes with bulk RNA-seq data in TCGA were subjected to screening. Preliminary screening identified 10 candidate progression-related genes, including CDH19, AQP5, SDR16C5, NCAN, TTYH1, XAGE2, RIMS2, GZMB, LY6D, and FAM3B. By checking their profiles using single-cell RNA-seq data, only CDH19, SDR16C5, TTYH1, and RIMS2 had expression in primary triple-negative breast cancer (TNBC) cells. Prognostic analysis only confirmed that RIMS2 expression was an independent prognostic indicator of favorable progression free survival (PFS) (HR: 0.78, 95%: 0.64–0.95, P 
= .015). GSEA analysis showed that low RIMS2 group expression had genes significantly enriched in DNA Repair, and MYC Targets V2. Among the 89 basal-like cells, RIMS2 expression was negatively correlated with DNA repair and epithelial-to-mesenchymal transition (EMT).

RIMS2 expression was negatively associated with DNA repair capability of basal-like breast tumor cells and might serve as an independent indicator of favorable PFS.
Endoscopic drainage for management of infected necrosis following EUS-TA in a patient with pancreatic cancer
Authors: Kim Young Jung , Cho Eunae , Park Chang Hwan
Published: April 2021

Rationale:

Endoscopic ultrasonography-guided tissue acquisition (EUS-TA) has become the norm for the diagnosis of pancreatic solid lesions. EUS-TA is relatively safe, but various complications can occur. Infected pancreatic necrosis (IPN) is a rare but serious complication. The latest guidelines suggest that all invasive interventions in patients with IPN should be delayed until walled-off necrosis appears.

Patient concerns:

A 73-year-old man was referred to our hospital with double primary cancers including gallbladder and pancreas. We performed EUS-TA on metastatic pancreatic tail cancer to confirm histologic diagnosis. Six days after the procedure, he developed abdominal pain and fever.

Diagnoses:

The patient's laboratory findings showed leukocytosis and C-reactive protein elevation. Fluid collection around pancreas tail and stomach was detected in computed tomography (CT) scan, and the patient was diagnosed with IPN.

Interventions and outcomes:

EUS-guided endoscopic transmural drainage (EUS-TD) was performed for the treatment of IPN. Two days after the procedure with antibiotics, his CRP level decreased abruptly, and he received chemotherapy for the treatment of pancreatic ductal adenocarcinoma (PDAC) 5 days after the procedure. He was discharged from our hospital without complications 15 days after chemotherapy.

Lessons:

In selected patients with PDAC, early endoscopic drainage may be recommended as treatment for IPN resulting from complications of EUS-TA.
Association between NEAT1 polymorphism and the risk of lung cancer
Authors: Hu Zhongbao , Chen Jingsheng , Meng Ping , Li Ming
Published: April 2021

Background:

Long noncoding RNAs play vital roles in development and progression of lung cancers. Nuclear paraspeckle assembly transcript 1 (NEAT1) polymorphisms were reported to be closely related to lung cancer susceptibility. Recently, numerous studies have been performed to detect the association between NEAT1 polymorphisms and lung cancer susceptibility. However, their results were inconsistent and controversial. So, we carried out a meta-analysis aiming to define the association exactly.

Methods:

Appropriate studies were retrieved from searching Web of Science, PubMed, Scopus, and Google scholar databases, updated January 31, 2021. The pooled odds ratios with 95% confidence intervals were calculated to estimate the strength of the association between NEAT1 polymorphisms and lung cancer risk. All of the data were analyzed with Stata 16.0.

Results:

The results of this meta-analysis will be submitted to a peer-reviewed journal for publication.

Conclusion:

This meta-analysis will summarize the relationship between NEAT1 polymorphism and lung cancer.
Ultrasound in patients with treated head and neck carcinomas
Authors: Jiang Hongying , Tan Qiling , He Fawei , Yang Wei , Liu Jifeng , Zhou Fang , Zhang Mingxia
Published: April 2021

Correct follow-up is necessary to avoid under- or overtreatment in the care of patients with treated carcinomas of head and neck. Ultrasound is a cost-effective, harmless, easy, and feasible method. It can be applied in the outpatient clinic in follow-up but the United Kingdom National Multidisciplinary guidelines are recommended computed tomography or magnetic resonance imaging for the detection of metastasis for head and neck carcinomas in the follow-up period. The purpose of the study was to state that neck ultrasound would be the method of choice on follow-up care of Chinese patients who received primary treatment for carcinoma of head and neck.

Patients who received primary treatment for carcinoma of the head and neck were examined for 5-years in follow-up through physical, clinical, and neck ultrasound (n = 198). If patients had no evidence of disease after 60 months of definitive therapy considered as a cure. If patients had no evidence of disease after 36 months of salvage therapy considered as a cure of recurrence.

Irrespective of definitive treatment used, the study was monitored through neck ultrasound during 5 years of a follow-up visit and was reported cure in 126 (64%) patients and recurrence in 72 (36%; distant metastasis: 33 [17%], local recurrence: 24 [12%], and regional recurrence: 15 [7%]) patients. Primary tumor stage IV, III, II, and I had 63% (15/24), 51% (21/41), 32% (18/56), and 23% (18/77) recurrence, respectively. The time to detect regional recurrence was shorter than that for local recurrence (P < .0001, q = 15.059) and distant recurrence (P < .0001, q = 7.958). Local recurrence and stage I primary tumor had the highest percentage cure for recurrence.

Neck ultrasound in the follow-up period is reported to be effective for the detection of recurrence of patients who received primary treatment for carcinoma of head and neck especially regional recurrence and primary tumor stage I.

Level of Evidence: III.
Subpleural ground glass opacities diagnosed by bronchoscopic brush cytology with manual mapping navigation
Authors: Zhang Lei , Wang Guiqi
Published: April 2021

Rationale:

Ground-glass opacity nodules (GGNs) are a computed tomography (CT) finding suggestive of lung cancer. Conventional bronchoscopy with brush cytology is a simple diagnostic modality but has a low diagnostic yield for peripheral lesions, especially peripheral GGNs. Therefore, maximizing the detection rate of bronchoscopic brushings should be a key objective. We report a case of a subpleural ground glass opacity (GGO) with a cytological diagnosis of adenocarcinoma by bronchoscopic brushing guided by manual mapping navigation.

Patient concerns:

A 46-year-old man was hospitalized for GGO in the right lung. Follow-up CT revealed a subpleural nodule sized 1.2 cm × 0.9 cm in the superior segment of the right lower lobe.

Diagnoses:

CT findings of the patient's nodule were suggestive of malignancy.

Interventions:

The patient underwent conventional bronchoscopy combined with brushing guided by manual mapping navigation, with subsequent cytological diagnosis of adenocarcinoma. The patient then underwent right lower lobectomy with mediastinal lymph node dissection.

Outcomes:

There were no postoperative complications. Postoperative pathological examination showed lung adenocarcinoma with lepidic and acinar growth without visceral pleural invasion (pT1aN0M0, IA1).

Lessons:

Exfoliated cells present in peripheral GGNs are rarely detected on brush sampling. However, use of a manual mapping navigation system may help increase the sensitivity of conventional bronchoscopic brushing for the diagnosis of peripheral pulmonary lesions.
Multimodal ultrasound imaging of primary thyroid schwannoma
Authors: Zhao Hai Na , Ma Bu Yun , Yan Feng , Peng Yu Lan
Published: April 2021

Rationale:

Primary schwannoma of the thyroid gland is very rare, and its preoperative diagnosis is difficult.

Patient concerns:

We report the case of a thyroid nodule in an 18-year-old woman, who presented with a mass in her left neck with stiffness and normal thyroid function. However, the patient complained of numbness in her left upper extremity, and ultrasound (US) features were suspicious of malignancy.

Diagnoses:

Multimodal US imaging was performed using B-mode, color doppler, ultrasonic elastography (UE), and contrast-enhanced ultrasound (CEUS). CEUS revealed heterogeneous enhancement and “target sign” within the tumor. The nodule was suspicious for malignancy and classified as TI-RADS 4b, while the elasticity values measured by UE indicated a benign lesion. Fine needle aspiration (FNA) was subsequently performed in the markedly contrast-enhanced area for biopsy. Cytological results revealed a benign schwannoma.

Intervention:

The patient underwent left lobe resection. Postoperative pathology confirmed it to be a primary benign schwannoma of the thyroid.

Outcomes:

After thyroidectomy, the patient was followed-up with US. At present, all laboratory tests and thyroid imaging are normal, and the numbness of the left upper limb has disappeared.

Lessons:

The combination of different US modalities is useful for the diagnosis of thyroid lesions. FNA performed under CEUS guidance improves the accuracy of biopsy sampling.
Clinical and genetic analysis of 2 rare cases of Wiskott–Aldrich syndrome from Chinese minorities
Authors: Liu Haifeng , Wang Yanchun , Li Yangfang , Tao Lvyan , Zhang Yu , He Xiaoli , Zhou Yuantao , Liu Xiaoning , Wang Yan , Li Li
Published: April 2021

Rationale:

Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by thrombocytopenia, small platelets, eczema, immunodeficiency, and an increased risk of autoimmunity and malignancies. X-linked thrombocytopenia (XLT), the milder phenotype of WAS, is always limited to thrombocytopenia with absent or slight infections and eczema. Here, we illustrated the clinical and molecular characteristics of 2 unrelated patients with WAS from Chinese minorities.

Patient concerns:

Patient 1, a 13-day-old male newborn of the Chinese Lahu minority, showed a classic WAS phenotype, including thrombocytopenia, small platelets, buttock eczema, and recurrent infections. Patient 2, an 8-year-and 8-month-old boy of the Chinese Zhuang minority, presented an XLT phenotype without eczema and repeated infections.

Diagnosis:

Next-generation sequencing was performed to investigate the genetic variations. Flow cytometry was used to quantify the expression of WAS protein and analyze the lymphocyte subsets. A novel frameshift WAS mutation (c.927delC, p.Q310Rfs∗135) and a known nonsense WAS mutation (c.1090C>T, p.R364X) were identified in Patient 1 and Patient 2, respectively. Both patients were confirmed to have WAS protein deficiency, which was more severe in Patient 1. Meanwhile, the analysis of lymphocyte subsets revealed an abnormality in Patient 1, but not in Patient 2. Combined with the above clinical data and genetic characteristics, Patient 1 and Patient 2 were diagnosed as classic WAS and XLT, respectively. In addition, many miliary nodules were accidentally found in abdominal cavity of Patient 2 during appendectomy. Subsequently, Patient 2 was confirmed with pulmonary and abdominal tuberculosis through further laboratory and imaging examinations. To our knowledge, there have been only a few reports about WAS/XLT with tuberculosis.

Interventions:

Both patients received anti-infection therapy, platelet transfusions, and intravenous immunoglobulins. Moreover, Patient 2 also received antituberculosis treatment with ethambutol and amoxicillin-clavulanate.

Outcomes:

The clinical symptoms and hematological parameters of these 2 patients were significantly improved. Regrettably, both patients discontinued the treatment for financial reasons.

Lessons:

Our report expands the pathogenic mutation spectrum of WAS gene and emphasizes the importance of molecular genetic testing in diagnosing WAS. Furthermore, researching and reporting rare cases of WAS from different populations will facilitate diagnosis and treatment of this disease.
The therapeutic effect and safety of the drugs for COVID-19
Authors: Qiu Rong , Li Jingwei , Xiao Yuxuan , Gao Ziyi , Weng Yihang , Zhang Qiran , Wang Chengdi , Gong Hanlin , Li Weimin
Published: April 2021

Background:

Coronavirus disease 2019 (COVID-19) has spread almost all regions of the world and caused great loss to the whole body of mankind. Thus, numerous clinical trials were conducted to find specific medicine for COVID-19 recently. However, it remains unanswered whether they are beneficial.

Objective:

This study aimed to evaluate the efficiency and safety of the COVID-19 medicine.

Methods:

Studies were determined through searching PubMed, Embase, Cochrane Library, and Medline. The studies of COVID-19 medicine were involved with eligible end points containing mortality, discharge rate, rate of clinical improvement, and rate of serious adverse events.

Results:

A total of 33 studies involving 37,879 patients were included in our study, whose intervening measures contained three major types of COVID-19 medicine, ACEI/ARB, antiviral medicine, and chloroquine/hydroxychloroquine. Compared to control group, COVID-19 drugs have no distinct effect on mortality (RR, 0.93; 95% CI, 0.79–1.11, P = .43) and discharge rate (RR, 1.06; 95% CI, 0.98–1.14, P = .13). However, antiviral medicine presents the obvious advantage in clinical improvement (RR, 1.11; 95% CI, 1.01–1.23, P < .05). In addition, the serious adverse events rate (RR, 0.75; 95% CI, 0.63–0.88, P < .05) of COVID-19 medicine is lower than control group.

Conclusion:

The results indicated antiviral medicine was potential specific medicine for COVID-19 treatment by improving clinical symptoms, but it failed to increase the discharge rate and reduce mortality. Chloroquine/hydroxychloroquine and ACEI/ARB had no significant effect on treatment of COVID-19, thus they were not recommended for routine medication. Moreover, more trials are needed to find effective drugs to lower the mortality of COVID-19 patients.
The predictive value of serum procalcitonin for non-invasive positive pressure ventilation in the patients with acute exacerbation of chronic obstructive pulmonary disease
Authors: Liu Linlin , Luan Ying , Xiao Ling , Wang Ning , Wang Jing , Cui Zhaobo
Published: April 2021

This study aimed to estimate the value of serum procalcitonin (PCT) for non-invasive positive pressure ventilation (NIPPV) prediction in the patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD).

A total of 220 AECOPD patients were divided into NIPPV group (n = 121) and control group (routine treatment, n = 99) based on the routine standards and physicians’ experience. Logistic regression analysis was performed to identify the independent factors for NIPPV treatment. Additionally, the predictive values of the factors were measured through receiver operation characteristic (ROC) curve.

NIPPV group and control group showed significant differences in respiratory rate (RR), PaO2, PaCO2, pH, oxygenation index, erythrocyte sedimentation rate (ESR), neutrophil, CRP (C-reaction protein), and PCT (P < .05 for all). PCT, CRP, PaCO2, RR, and neutrophil were independently correlated with NIPPV treatment in AECOPD. ROC curve showed that PCT had superior predictive value, with AUC of 0.899, the sensitivity of 86%, and the specificity of 91.9%. The cut-off value of serum PCT for NIPPV prediction was 88.50 ng/l.

AECOPD patients who require NIPPV treatment frequently have high levels of PCT, CRP, PaCO2, RR and neutrophil. Serum PCT may be employed as an indicator for NIPPV treatment in AECOPD patients.