bluuebunny/crossref_metadata_2025 huggingface dataset:
The balance function is associated with frailty in community-dwelling older women
Authors: Shinohara Tomoyuki , Saida Kosuke , Miyata Kazuhiro , Usuda Shigeru
Published: January 2021

Conditions underlying balance impairment should be identified to improve knowledge regarding clinical interventions for frail older adults. This study aims to explore the relationship between balance functions and frailty by using the brief balance evaluation systems test (BESTest), which can assess biomechanical constraints, stability limits/verticality, anticipatory postural adjustments (APAs), reactive postural responses, sensory orientation and stability in gait. A total of 75 community-dwelling older women were included in this cross-sectional study. We evaluated frailty by using the Kihon checklist and assessed the participants’ balance functions by using the Brief BESTest. We performed the Mann–Whitney U test and receiver operating characteristic curve analysis to compare each balance function between frail and nonfrail participants. Twenty-two of the 75 (29.3%) participants were included in the frailty group. We noted significant differences between the frailty and nonfrailty groups with regard to stability limit, APAs, sensory orientation, and stability in gait (P = 0.010, 0.001, 0.008 and <0.001, respectively). In terms of determining frailty and nonfrailty, APAs and stability in gait were moderately accurate (the area under the curve = 0.730 and 0.713, respectively). APAs showed the highest sensitivity (0.864), whereas stability limits, sensory orientation, and stability in gait showed the highest specificity (0.943, 0.849 and 0.868, respectively). Thus, frail and nonfrail older adults showed significantly different balance functions, such as stability limits, APAs, sensory orientation and stability in gait. The Brief BESTest is useful for evaluating balance functions in relation to frailty.
The Effect of a Psychotherapy Protocol on Dream Awareness in Adults With Generalized Anxiety Disorder
Authors: Khodarahimi Siamak , Mirderikvand Fazlolah , Amraei Kourosh
Published: January 2021

This study aimed to examine the effect of an Affective and Sensory Psychotherapy Protocol (ASPP) on dream awareness in adults with generalized anxiety disorder (GAD). For this purpose, 60 self-referred male and female adults were studied within a randomized clinical trial. The Generalized Anxiety Disorder 7-Item Scale and the Mannheim Dream Questionnaire were used at baseline, posttreatment, and 3-month follow-up. No significant difference was observed between patients in the experimental and control groups at baseline. Findings showed that patients in the experimental group had a significant increase in dream recall, attitude toward dreams, and the total dream score than individuals in the control group. However, no sex difference was observed in the results for within-subject and between-group effects in the current study. The present research supported the influence of an ASPP on dream awareness in adults with GAD.
Postmortem Findings Associated With SARS-CoV-2
Authors: Satturwar Swati , Fowkes Mary , Farver Carol , Wilson Allecia M. , Eccher Albino , Girolami Ilaria , Pujadas Elisabet , Bryce Clare , Salem Fadi , El Jamal Siraj M. , Paniz-Mondolfi Alberto , Petersen Bruce , Gordon Ronald E. , Reidy Jason , Fraggetta Filippo , Marshall Desiree A. , Pantanowitz Liron
Published: January 2021

Coronavirus Disease 2019 (COVID-19), caused by the novel Severe Acute Respiratory Syndrome–associated Coronavirus 2 (SARS-CoV-2), has become a global threat to public health. COVID-19 is more pathogenic and infectious than the prior 2002 pandemic caused by SARS-CoV-1. The pathogenesis of certain disease manifestations in COVID-19 such as diffuse alveolar damage (DAD) are thought to be similar to SARS-CoV-1. However, the exact pathogenesis of COVID-19 related deaths remains poorly understood. The aim of this article was to systematically summarize the rapidly emerging literature regarding COVID-19 autopsies. A meta-analysis was also conducted based on data accrued from preprint and published articles on COVID-19 (n=241 patients) and the results compared with postmortem findings associated with SARS-CoV-1 deaths (n=91 patients). Both autopsy groups included mostly adults of median age 70 years with COVID-19 and 50 years with SARS-CoV-1. Overall, prevalence of DAD was more common in SARS-CoV-1 (100.0%) than COVID-19 (80.9%) autopsies (P=0.001). Extrapulmonary findings among both groups were not statistically significant except for hepatic necrosis (P <0.001), splenic necrosis (P<0.006) and white pulp depletion (P <0.001) that were more common with SARS-CoV-1. Remarkable postmortem findings in association with COVID-19 apart from DAD include pulmonary hemorrhage, viral cytopathic effect within pneumocytes, thromboembolism, brain infarction, endotheliitis, acute renal tubular damage, white pulp depletion of the spleen, cardiac myocyte necrosis, megakaryocyte recruitment, and hemophagocytosis.
Evaluation and Pathologic Classification of Choledochal Cysts
Authors: Aydin Mericöz Cisel , Hacihasanoglu Ezgi , Muraki Takashi , Pehlivanoglu Burcin , Memis Bahar , Mittal Pardeep , Polito Humbert , Saka Burcu , Everett Rhonda , Sarmiento Juan , Kooby David , Maithel Shishir K. , Erkan Mert , Basturk Olca , Reid Michelle D. , Adsay Volkan
Published: January 2021

Choledochal cyst (CC) is believed to be a mostly Asian disorder. As a clinically defined entity, its pathologic correlates are poorly characterized. Eighty-four resected CCs from the West were reanalyzed. After applying established Japanese criteria, 9/66 with available imaging were disqualified and 10/39 with preoperative cyst typing had to be recategorized. None had been diagnosed with, or evaluated for, pancreatobiliary maljunction, but on retrospective analysis of radiologic images, 12/66 were found to have pancreatobiliary maljunction. The clinical findings were: F/M=5.7; mean age, 48; most (77%) presented with abdominal pain; mean size, 2.9 cm; choledocholithiasis 11%. Gross/histologic examination revealed 3 distinct pathology-based categories: (I) Cystic dilatation of native ducts (81%). (II) Double bile duct (13%), almost all of which were found in women (10/11); all were diagnosed by pathologic examination, and not preoperative diagnosis. (III) Gastrointestinal (GI) duplication type (6%). Microscopic findings of the entire cohort included mucosal-predominant lymphoplasmacytic inflammation (50%), follicular cholangitis (7%), mucosal hyperplasia (43%; 13% with papillae), intestinal metaplasia (10%), BilIN-like hyperplasia (17%), erosion/ulceration (13%), and severe dysplasia-mimicking atypia including “detachment atypia” and micropapillary degeneration (11%). Carcinomatous changes were seen in 14 cases (17%) (high-grade dysplasia/carcinoma in situ in 7, intraductal papillary neoplasm 1, and invasive carcinoma 6); and 13/14 of these occurred in pathologic category I, all with cyst size >1 cm. In conclusion, diagnostic imaging guidelines used in Asia are not routinely used (but should be adopted) in the West. Pathologically, cases designated as CC are classifiable in 3 groups: category 1 (dilated native duct type), more prone to carcinomatous change; category 2, double-duct phenomenon (all but 1 being female in this study); and category 3, GI-type duplication. Overall, 17% of CCs show carcinomatous change (50% of them invasive). CC specimens should be carefully examined with this classification and submitted entirely for assessment of at-risk mucosa and cancerous transformation.
Prevalence and Clinicopathologic Features of Intestinal Perforation Caused by Segmental Absence of the Intestinal Musculature in Adults
Authors: Tsuyuki Takuji , Satou Akira , Takahara Taishi , Nakajima Kosei , Tsuzuki Toyonori
Published: January 2021

Segmental absence of the intestinal musculature (SAIM) can cause intestinal perforation in adults. However, its prevalence and clinicopathologic features have not been well-described. This study aimed to determine the prevalence of SAIM-associated perforation and characterize its clinicopathologic features. We retrospectively examined 109 cases of intestinal perforation that underwent surgical resection from January 2009 to December 2019. SAIM was defined as the complete absence of the muscularis propria without extensive inflammation and fibrinous exudation around the perforation. SAIM was the second most frequent cause of perforation (26 cases: 24%), the most frequent cause being related to diverticulitis (39 cases: 36%). The most common site was the sigmoid colon (12 cases: 46.2%). The younger group (aged below 65 y) exhibited more frequent perforation of the upper segments of the gastrointestinal tract (from the duodenum to the descending colon) than the older group (65 y and above) (P=0.0018). No patients developed recurrence. The most common gross features were well-defined circular or small punched-out lesions, and the histologic features were complete absence of the muscularis propria and absence of hemorrhage and necrosis around the area of perforation. The characteristic features of SAIM were unique and their prevalence was higher than previously reported. The precise recognition of SAIM can aid in understanding the cause of perforation and avoiding further unnecessary examinations.
Distinct Small Intestine Mast Cell Histologic Changes in Patients With Hereditary Alpha-tryptasemia and Mast Cell Activation Syndrome
Authors: Hamilton Matthew J. , Zhao Melissa , Giannetti Matthew P. , Weller Emily , Hufdhi Raied , Novak Peter , Mendoza-Alvarez Lybil B. , Hornick Jason , Lyons Jonathan J. , Glover Sarah C. , Castells Mariana C. , Pozdnyakova Olga
Published: January 2021

Mast cells (MCs) are important in intestinal homeostasis and pathogen defense but are also implicated in many of the clinical manifestations in disorders such as irritable bowel syndrome. The utility of specific staining for MCs to quantify and phenotype them in intestinal biopsies in patients with gastrointestinal (GI) symptoms is controversial and is not a widely adopted practice. Whether or not intestinal MCs are increased or have a unique phenotype in individuals with hereditary alpha-tryptasemia (HαT), who have extra copies of the MC tryptase gene TPSAB1 and typically elevated baseline serum tryptase levels >8 ng/mL is not known. We examined the duodenal biopsies of 17 patients with HαT and compared them to 15 patients with mast cell activation syndrome who had baseline serum tryptases <8 ng/mL (MCAS-NT) and 12 GI-controls. We determined that the HαT subjects had increased MCs in the duodenum compared with MCAS-NT and GI-controls (median=30.0; interquartile range [IQR]: 20.0 to 40.0 vs. median=15.0; IQR: 5.00 to 20.0; P=0.013 and median=15.0; IQR: 13.8 to 20.0; P=0.004, respectively). These MCs were significantly found in clusters (<15 MCs) and were located throughout the mucosa and submucosa including the superficial villi compared with MCAS-NT and GI-control patients. Spindle-shaped MCs were observed in all groups including controls. These data demonstrate that HαT is associated with increased small intestinal MCs that may contribute to the prevalent GI manifestations observed among individuals with this genetic trait.
Integrating Focused Cardiac Ultrasound Into Pediatric Septic Shock Assessment*
Authors: Arnoldi Sara , Glau Christie L. , Walker Sarah B. , Himebauch Adam S. , Parikh Darshana S. , Udeh Simone C. , Weiss Scott L. , Fitzgerald Julie C. , Nishisaki Akira , Conlon Thomas W.
Published: January 2021

Objectives:

To assess focused cardiac ultrasound impact on clinician hemodynamic characterization of patients with suspected septic shock as well as expert-generated focused cardiac ultrasound algorithm performance.

Design:

Retrospective, observational study.

Setting:

Single-center, noncardiac PICU.

Patients:

Less than 18 years old receiving focused cardiac ultrasound study within 72 hours of sepsis pathway initiation from January 2014 to December 2016.

Interventions:

Hemodynamics of patients with suspected septic shock were characterized as fluid responsive, myocardial dysfunction, obstructive physiology, and/or reduced systemic vascular resistance by a bedside clinician before and immediately following focused cardiac ultrasound performance. The clinician’s post-focused cardiac ultrasound hemodynamic assessments were compared with an expert-derived focused cardiac ultrasound algorithmic hemodynamic interpretation. Subsequent clinical management was assessed for alignment with focused cardiac ultrasound characterization and association with patient outcomes.

Measurements and Main Results:

Seventy-one patients with suspected septic shock (median, 4.7 yr; interquartile range, 1.6–8.1) received clinician performed focused cardiac ultrasound study within 72 hours of sepsis pathway initiation (median, 2.1 hr; interquartile range, –1.5 to 11.8 hr). Two patients did not have pre-focused cardiac ultrasound and 23 patients did not have post-focused cardiac ultrasound hemodynamic characterization by clinicians resulting in exclusion from related analyses. Post-focused cardiac ultrasound clinician hemodynamic characterization differed from pre-focused cardiac ultrasound characterization in 67% of patients (31/46). There was substantial concordance between clinician’s post-focused cardiac ultrasound and algorithm hemodynamic characterization (33/48; κ = 0.66; CI, 0.51–0.80). Fluid responsive (κ = 0.62; CI, 0.40–0.84), obstructive physiology (к = 0.87; CI, 0.64–1.00), and myocardial dysfunction (1.00; CI, 1.00–1.00) demonstrated substantial to perfect concordance. Management within 4 hours of focused cardiac ultrasound aligned with algorithm characterization in 53 of 71 patients (75%). Patients with aligned management were less likely to have a complicated course (14/52, 27%) compared with misaligned management (8/19, 42%; p = 0.25).

Conclusions:

Incorporation of focused cardiac ultrasound in the evaluation of patients with suspected septic shock frequently changed a clinician’s characterization of hemodynamics. An expert-developed algorithm had substantial concordance with a clinician’s post-focused cardiac ultrasound hemodynamic characterization. Management aligned with algorithm characterization may improve outcomes in children with suspected septic shock.
Pain during and after COVID-19 in Germany and worldwide: a narrative review of current knowledge
Authors: Meyer-Frießem Christine H. , Gierthmühlen Janne , Baron Ralf , Sommer Claudia , Üçeyler Nurcan , Enax-Krumova Elena K.
Published: January 2021

Pain is a common symptom accompanying the coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Nonspecific discomfort such as sore throat and body ache are frequent. Parainfectious pain such as headache, myalgia, or neuropathic pain has also been reported. The latter seems to be associated with an autoimmune response or an affection of the peripheral neuromuscular system or the central nervous system because of the viral infection. Furthermore, chronic pain can be a complication of intensive care unit treatment due to COVID-19 itself (such as intensive care–acquired weakness) or of secondary diseases associated with the SARS-CoV-2 infection, including Guillain–Barré syndrome, polyneuritis, critical illness polyneuropathy, or central pain following cerebrovascular events. Data on long-lasting painful symptoms after clinically manifest COVID-19 and their consequences are lacking. In addition, preexisting chronic pain may be exacerbated by limited and disrupted health care and the psychological burden of the COVID-19 pandemic. Medical providers should be vigilant on pain during and after COVID-19.
Automated Detection and Quantification of COVID-19 Airspace Disease on Chest Radiographs
Authors: Mortani Barbosa Eduardo J. , Gefter Warren B. , Ghesu Florin C. , Liu Siqi , Mailhe Boris , Mansoor Awais , Grbic Sasa , Vogt Sebastian
Published: January 2021

Objectives

The aim of this study was to leverage volumetric quantification of airspace disease (AD) derived from a superior modality (computed tomography [CT]) serving as ground truth, projected onto digitally reconstructed radiographs (DRRs) to (1) train a convolutional neural network (CNN) to quantify AD on paired chest radiographs (CXRs) and CTs, and (2) compare the DRR-trained CNN to expert human readers in the CXR evaluation of patients with confirmed COVID-19.

Materials and Methods

We retrospectively selected a cohort of 86 COVID-19 patients (with positive reverse transcriptase-polymerase chain reaction test results) from March to May 2020 at a tertiary hospital in the northeastern United States, who underwent chest CT and CXR within 48 hours. The ground-truth volumetric percentage of COVID-19-related AD (POv) was established by manual AD segmentation on CT. The resulting 3-dimensional masks were projected into 2-dimensional anterior-posterior DRR to compute area-based AD percentage (POa). A CNN was trained with DRR images generated from a larger-scale CT dataset of COVID-19 and non-COVID-19 patients, automatically segmenting lungs, AD, and quantifying POa on CXR. The CNN POa results were compared with POa quantified on CXR by 2 expert readers and to the POv ground truth, by computing correlations and mean absolute errors.

Results

Bootstrap mean absolute error and correlations between POa and POv were 11.98% (11.05%–12.47%) and 0.77 (0.70–0.82) for average of expert readers and 9.56% to 9.78% (8.83%–10.22%) and 0.78 to 0.81 (0.73–0.85) for the CNN, respectively.

Conclusions

Our CNN trained with DRR using CT-derived airspace quantification achieved expert radiologist level of accuracy in the quantification of AD on CXR in patients with positive reverse transcriptase-polymerase chain reaction test results for COVID-19.
Association Between Converting Asystole From Initial Shockable ECG Rhythm Before Extracorporeal Cardiopulmonary Resuscitation and Outcome
Authors: Maeda Keisuke , Inoue Akihiko , Kuroda Yasuhiro , Inoue Fumiya , Suga Masafumi , Ijuin Shinichi , Kai Soichiro , Koga Tokito , Igarashi Nobuaki , Matsuyama Shigenari , Kawase Tetsunori , Ishihara Satoshi , Naitou Hiroshi , Nakayama Shinichi
Published: January 2021

Background:

Initial electrocardiogram (ECG) rhythm is a predictor of outcomes in out-of-hospital cardiac arrest (OHCA) in patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). However, ECG rhythm often changes before ECPR, and the consequence of this change remains unclear. This study aimed to assess the relationship between the conversion of ECG rhythm from initial shockable rhythm before ECPR and mortality.

Patients and Methods:

This was a retrospective cohort study of OHCA patients with initial shockable rhythm who underwent ECPR between January 2010 and September 2020. Patients were classified into two groups: asystole (patients whose ECG rhythm converted to asystole at any time before initiating ECPR) and non-asystole (patients whose ECG rhythm did not convert to asystole at any time before initiating ECPR) groups. The primary outcome was in-hospital mortality.

Results:

A total of 102 patients were included in the study; in-hospital mortality rate was 46.1% (n = 47) and 76 (74.5%) patients had unfavorable neurological outcomes (Cerebral Performance Category: 3–5). There were 33 and 69 patients in the asystole and non-asystole groups, respectively. The mortality rates in the asystole and non-asystole groups were 69.7% and 34.8%, respectively (P = 0.001). On multivariable analysis, the asystole group showed a significant association with mortality (odds ratio, 5.42; 95% confidence interval, 2.11–15.36; P < 0.001).

Conclusion:

Conversion to asystole before ECPR at any time in patients with OHCA is associated with mortality in patients with an initial shockable ECG rhythm.
CX3CR1 Depletion Promotes the Formation of Platelet–Neutrophil Complexes and Aggravates Acute Peritonitis
Authors: Ngamsri Kristian-Christos , Böhne Jan , Simelitidis Mariana-Sophie , Gamper-Tsigaras Jutta , Zhang Yi , Ehnert Sabrina , Konrad Franziska M.
Published: January 2021

Background:

Peritonitis is a life-threatening condition on intensive care units. Inflammatory cytokines and their receptors drive inflammation, cause the formation of platelet–neutrophil complexes (PNCs) and therefore the migration of polymorphonuclear neutrophils (PMNs) into the inflamed tissue. CX3CL1 and its receptor CX3CR1 are expressed in various cells, and promote inflammation. The shedding of CX3CL1 is mediated by a disintegrin and metalloprotease (ADAM) 17. The role of the CX3CL1-CX3CR1 axis in acute peritonitis remains elusive.

Methods:

In zymosan-induced peritonitis, we determined the formation of PNCs in the blood and the expression of PNC-related molecules on PNCs. PMN migration into the peritoneal lavage was evaluated in wild-type (WT) and CX3CR1-/- animals by flow cytometry. CX3CL1, ADAM17, and the expression of various inflammatory cytokines were detected. Further, we determined the inflammation-associated activation of the intracellular transcription factor extracellular signal-regulated kinase 1/2 (ERK1/2) by Western blot.

Results:

The PMN accumulation in the peritoneal lavage and the PNC formation in the circulation were significantly raised in CX3CR1-/- compared with WT animals. The expression of PNC-related selectins on PNCs was significantly increased in the blood of CX3CR1-/- animals, as well as cytokine levels. Further, we observed an increased activation of ERK1/2 and elevated ADAM17 expression in CX3CR1-/- during acute inflammation. Selective ERK1/2 inhibition ameliorated inflammation-related increased ADAM17 expression.

Conclusions:

A CX3CR1 deficiency raised the release of inflammatory cytokines and increased the PNC formation respectively PMN migration via an elevated ERK1/2 activation during acute peritonitis. Further, we observed a link between the ERK1/2 activation and an elevated ADAM17 expression on PNC-related platelets and PMNs during inflammation. Our data thus illustrate a crucial role of CX3CR1 on the formation of PNCs and regulating inflammation in acute peritonitis.
Evaluation of Recombinant Herpes Zoster Vaccine for Primary Immunization of Varicella-seronegative Transplant Recipients
Authors: L'Huillier Arnaud G. , Hirzel Cedric , Ferreira Victor H. , Ierullo Matthew , Ku Terrance , Selzner Nazia , Schiff Jeffrey , Juvet Stephen , Miao Congrong , Schmid D. Scott , Humar Atul , Kumar Deepali
Published: January 2021

Background.

Immunization of varicella-zoster virus (VZV)-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV-seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection.

Methods.

VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2–6 mo apart. Blood was drawn prevaccination (V1), before the second dose (V2), and 4 wk after the second dose (V3). Humoral immunity (anti-glycoprotein E) and cell-mediated immunity were evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines.

Results.

Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 y and median time since transplant procedure was 3.8 y. The most frequent transplant types were liver (35%) and lung (30%). Median anti-glycoprotein E levels significantly increased from V1 to V3 (P = 0.001) and V2 to V3 (P < 0.001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cell counts increased from V1 to V2 (54/106 versus 104/106 cells; P = 0.041) and from V2 to V3 (380/106; P = 0.002). Most adverse events were mild with no rejection episodes.

Conclusions.

RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients and has the potential to be considered as a preventive strategy against primary varicella.
Secundilactobacillus folii sp. nov., isolated from fermented tea leaves in Thailand
Authors: Phuengjayaem Sukanya , Nuhwa Ratthanatda , Phongsopitanun Wongsakorn , Tanasupawat Somboon
Published: January 2021

A Gram-stain-positive, catalase-negative, rod-shaped, non-motile, non-spore-forming, and facultatively anaerobic strain CRM56-3T, isolated from fermented tea leaves collected from Chiang Rai province, Thailand, was characterized based on a polyphasic approach. The strain produced dl-lactic acid heterofermentatively from glucose. It grew at 15–42 °C (optimum at 30 °C), pH 3.5–8.0 (optimum pH 6.0) and in 1–4 % (w/v) NaCl. Strain CRM56-3T contained C16:0, C19:0 cyclo ω8c, and C18:1
ω7c, and/or C18:1
ω6c as major cellular fatty acids. Based on 16S rRNA gene sequence analysis, strain CRM56-3T belongs to the genus

Secundilactobacillus

and was closely related to

Secundilactobacillus odoratitofui

DSM 19909T (99.2 %),

S. collinoides

JCM 1123T (98.9 %), and

S. paracollinoides

DSM 15502T (98.7 %). The draft genome of strain CRM56-3T contained 2681617 bp with 2413 coding sequences and DNA G+C content determined from genome sequence of 44.5 mol%. The digital DNA–DNA hybridization (dDDH) between strain CRM56-3T and

S. odoratitofui

DSM 19909T,

S. collinoides

JCM 1123T, and

S. paracollinoides

DSM 15502T were 19.5, 20.4, and 21.6 %, respectively. The average nucleotide identity (ANIm) and the average amino acid identity (AAI) between strain CRM56-3T and closely related strains were lower than 85.0 and 80.0 %, respectively. The strain CRM56-3T was clearly distinguished from related

Secundilactobacillus

species by its phenotypic and chemotaxonomic characteristics, 16S rRNA gene sequence similarity, and the draft genome analysis. Therefore, the strain represents a novel species of the genus Secundilactobacillus, for which the name of Secundilactobacillus folii sp. nov. is proposed. The type strain is CRM56-3T (=JCM 34223T=LMG 31663T=TISTR 2851T).
Evaluating Data-Driven Forecasting Methods for Predicting SARS-CoV2 Cases: Evidence From 173 Countries
Authors: Ahmad Ghufran , Ahmed Furqan , Rizwan Suhail , Muhammad Javed , Fatima Hira , Ikram Aamer , Zeeb Hajo
Published: January 2021

The WHO announced the epidemic of SARS-CoV2 as a public health emergency of international concern on 30th January 2020. To date, it has spread to more than 200 countries, and has been declared as a global pandemic. For appropriate preparedness, containment, and mitigation response, the stakeholders and policymakers require prior guidance on the propagation of SARS-CoV2. This study aims to provide such guidance by forecasting the cumulative COVID-19 cases up to 4 weeks ahead for 173 countries, using four data-driven methodologies; autoregressive integrated moving average (ARIMA), exponential smoothing model (ETS), random walk forecasts (RWF) with and without drift. We also evaluate the accuracy of these forecasts using the Mean Absolute Percentage Error (MAPE). The results show that the ARIMA and ETS methods outperform the other two forecasting methods. Additionally, using these forecasts, we generated heat maps to provide a pictorial representation of the countries at risk of having an increase in cases in the coming 4 weeks for June. Due to limited data availability during the ongoing pandemic, less data-hungry forecasting models like ARIMA and ETS can help in anticipating the future burden of SARS-CoV2 on healthcare systems.
Whole plastid genome-based phylogenomics supports an inner placement of theO. insectiferagroup rather than a basal position in the rapidly diversifyingOphrysgenus (Orchidaceae)
Authors: Bertrand Joris A. M. , Gibert Anaïs , Llauro Christel , Panaud Olivier
Published: January 2021

Some lineages of the Orchid genusOphrysexhibit among the highest diversification rates reported so far. As a consequence of a such intense and rapid evolution, the systematics and the taxonomy of this genus remains unclear. A hybrid assembly approach based-on long- and short-read genomic data allowed us to outperform classical methods to successfully assemble whole plastid genomes for two newOphrys species:O.aymoniniiandO.lutea. Along with three other previouslyOphrysplastid genome sequences, we then reconstructed the first whole plastome-based molecular phylogeny including representatives of the three mains recognizedOphryslineages. Our results support the placement of theO.insectiferaclade as sister group of ‘non-basalOphrys’ rather than a basal position. Our findings corroborate recent results obtained from genomic data (RAD-seq and transcriptomes) but contrast with previous ones. These results therefore confirm that molecular phylogenetic hypotheses based on a limited number ofloci(e.g.nrITS, matK, rbcL) may have provided a biased picture of phylogenetic relationships withinOphrysand possibly other plant taxa.
Evaluating the Long-Term Efficacy of COVID-19 Vaccines
Authors: Lin Dan-Yu , Zeng Donglin , Gilbert Peter B.
Published: January 2021

Large-scale deployment of safe and durably effective vaccines can curtail the COVID-19 pandemic.1−3However, the high vaccine efficacy (VE) reported by ongoing phase 3 placebo-controlled clinical trials is based on a median follow-up time of only about two months4−5and thus does not pertain to long-term efficacy. To evaluate the duration of protection while allowing trial participants timely access to efficacious vaccine, investigators can sequentially cross participants over from the placebo arm to the vaccine arm according to priority groups. Here, we show how to estimate potentially time-varying placebo-controlled VE in this type of staggered vaccination of participants. In addition, we compare the performance of blinded and unblinded crossover designs in estimating long-term VE.

Authors’ Information

Dan-Yu Lin, Ph.D., is Dennis Gillings Distinguished Professor of Biostatistics, and Donglin Zeng, Ph.D., is Professor of Biostatistics, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC 27599-7420, USA. Peter B. Gilbert, Ph.D., is Member, Vaccine and Infectious Disease Division, Fred Hutch, Seattle, WA 98109-1024, USA.

We show how to estimate the potentially waning long-term efficacy of COVID-19 vaccines using data from randomized, placebo-controlled clinical trials with staggered enrollment of participants and sequential crossover of placebo recipients.
KSR1- and ERK-dependent Translational Regulation of the Epithelial-to-Mesenchymal Transition
Authors: Rao Chaitra , Frodyma Danielle E. , Southekal Siddesh , Svoboda Robert A. , Black Adrian R. , Guda Chittibabu , Mizutani Tomohiro , Clevers Hans , Johnson Keith R. , Fisher Kurt W. , Lewis Robert E.
Published: January 2021

The epithelial-to-mesenchymal transition (EMT) is considered a transcriptional process that induces a switch in cells from a polarized state to a migratory phenotype. Here we show that KSR1 and ERK promote EMT through the preferential translation of Epithelial-Stromal Interaction 1 (EPSTI1), which is required to induce the switch from E-to N-cadherin and coordinate migratory and invasive behavior. EPSTI1 is overexpressed in human colorectal cancer (CRC) cells. Disruption of KSR1 or EPSTI1 significantly impairs cell migration and invasioninvitro, and reverses EMT, in part, by decreasing the expression of N-cadherin and the transcriptional repressors of E-cadherin expression, ZEB1 and Slug. In CRC cells lacking KSR1, ectopic EPSTI1 expression restored the E-to N-cadherin switch, migration, invasion, and anchorage-independent growth. KSR1-dependent induction of EMT via selective translation of mRNAs reveals its underappreciated role in remodeling the translational landscape of CRC cells to promote their migratory and invasive behavior.
Characterization of influenza vaccination recommendation across spatial scales in the United States
Authors: Kuney Madeline C. , Zipfel Casey M. , Bansal Shweta
Published: January 2021

The US public health system is organized in 3 levels: national, state-level, and county-level. Public health messaging both within and across these scales may not always be consistent, and for transmissible public health threats where cases in one spatial location may impact other areas, this lack of consistency could create problems. Here, we collected and analyzed data on influenza vaccination recommendations across public health administration levels. We assess spatial heterogeneity at the county level, and analyze consistency in recommendations across spatial scales. We also compare information accessibility with influenza vaccine affordability and availability to identify factors that may be most related to vaccine uptake. We find that influenza vaccine recommendations are highly variable in both their priority group specificity and in their ease of access, and there is poor agreement across spatial scales. This lack of consistency results in a lack of clear relationship between vaccination information and vaccine uptake. This work highlights the need for greater consistency in specific, easily accessed public health information from trusted sources.
Luminal nutrients activate distinct patterns in submucosal and myenteric neurons in the mouse small intestine
Authors: Fung C. , Hao M.M. , Obata Y. , Tack J. , Pachnis V. , Boesmans W. , Vanden Berghe P.
Published: January 2021

Nutrient signals sensed by enteroendocrine cells are conveyed to the enteric nervous system (ENS) to initiate intestinal reflexes. We addressed whether there are specific enteric pathways dedicated to detecting different luminal nutrients. Calcium imaging was performed on intact jejunal preparations from Wnt1-cre;R26R-GCaMP3 and Villin-cre;R26R-GCaMP3 mice which express a fluorescent calcium indicator in their ENS or intestinal epithelium, respectively. Glucose, acetate, and L-phenylalanine were perfused onto the mucosa whilst imaging underlying enteric neurons. Nutrient transport or diffusion across the mucosa was mimicked by applying nutrients onto sensory nerve endings in a villus, or onto myenteric ganglia. The nutrients perfused onto the mucosa each elicited Ca2+transients in submucosal neurons and in distinct patterns of myenteric neurons. Notably, the neurochemical subtypes of myenteric neurons that responded differed between the nutrients, while submucosal responders were predominantly cholinergic. Nutrients applied into villi or onto ganglia did not elicit specific neuronal responses but did stimulate Ca2+signaling in the mucosal epithelium. These data suggest that nutrients are first detected at the level of the epithelium and that the ENS is capable of discriminating between different compositions of luminal content. Furthermore, our data show that responses to mucosal stimulation are primarily in the myenteric plexus and submucosal neurons respond secondarily.
Neuropsychological assessment and virtual reality training of social prediction in patients with cerebellar malformation
Authors: Urgesi Cosimo , Butti Niccolò , Finisguerra Alessandra , Biffi Emilia , Valente Enza Maria , Romaniello Romina , Borgatti Renato
Published: January 2021

It has been proposed that impairments of the predictive function exerted by the cerebellum may account for social cognition deficits. Here, we integrated cerebellar functions in a predictive coding framework to elucidate how cerebellar alterations could affect the predictive processing of others’ behavior. Experiment 1 demonstrated that cerebellar patients were impaired in relying on contextual information during action prediction, and this impairment was significantly associated with social cognition abilities. Experiment 2 indicated that patients with cerebellar malformation showed a domain-general deficit in using contextual information to predict both social and physical events. Experiment 3 provided first evidence that a social-prediction training in virtual reality could boost the ability to use context-based predictions to understand others’ intentions. These findings shed new light on the predictive role of the cerebellum and its contribution to social cognition, paving the way for new approaches to the rehabilitation of the Cerebellar Cognitive Affective Syndrome.
Modeling Brain Connectivity Dynamics in Functional Magnetic Resonance Imaging via Particle Filtering
Authors: Ambrosi Pierfrancesco , Costagli Mauro , Kuruoğlu Ercan E , Biagi Laura , Buonincontri Guido , Tosetti Michela
Published: January 2021

Interest in the studying of functional connections in the brain has grown considerably in the last decades, as many studies have pointed out that these interactions can play a role as markers of neurological diseases. Most studies in this field treat the brain network as a system of connections stationary in time, but dynamic features of brain connectivity can provide useful information, both on physiology and pathological conditions of the brain. In this paper, we propose the application of a computational methodology, named Particle Filter (PF), to study non-stationarities in brain connectivity in functional Magnetic Resonance Imaging (fMRI). The PF algorithm estimates time-varying hidden parameters of a first-order linear time-varying Vector Autoregressive model (VAR) through a Sequential Monte Carlo strategy. On simulated time series, the PF approach effectively detected and enabled to follow time-varying hidden parameters and it captured causal relationships among signals. The method was also applied to real fMRI data, acquired in presence of periodic tactile or visual stimulations, in different sessions. On these data, the PF estimates were consistent with current knowledge on brain functioning. Most importantly, the approach enabled to detect statistically significant modulations in the cause-effect relationship between brain areas, which correlated with the underlying visual stimulation pattern presented during the acquisition.
PEBP regulates balance between apoptosis and autophagy, enabling coexistence of arbovirus and insect vector
Authors: Wang Shifan , Guo Huijuan , Zhu-Salzman Keyan , Ge Feng , Sun Yucheng
Published: January 2021

Apoptosis and autophagy are two most prominent forms of programmed cell deaths (PCD) that have been implicated in antiviral immunity in vertebrate and plant hosts. Arboviruses are able to coexist with its arthropod vectors by coordinating the PCD immunity, but the regulatory mechanism involved is largely unknown. We found that the coat protein (CP) of an insect-borne plant virus TYLCV directly interacted with a phosphatidylethanolamine-binding protein (PEBP) of its insect vector whitefly to negatively influence the MAPK signaling cascade. As a result, the apoptosis was activated in whitefly which increased viral loading. Simultaneously, the PEBP4-CP interaction liberated ATG8, the hallmark of autophagy initiation, and eliminates arbovirus. Furthermore, apoptosis-promoted virus loading was compromised by agonist-induced autophagy, but autophagy-associated suppression on virus loading was unaffected by apoptosis agonist or inhibitor, suggesting that virus loading was predominantly determined by autophagy rather than by apoptosis. Our results demonstrated that maintaining a mild immune response by coordinating apoptosis and autophagy processes presumably could facilitate coexistence of the arbovirus and its insect vector. Taken together, immune homeostasis shaped by two types of PCD may facilitate the arbovirus preservation within the insect vector.

Graphical abstract

Highlights

Interaction between whitefly PEBP4 and TYLCV CP suppresses phosphorylation of MAPK cascade, activating apoptosis

TYLCV CP liberates PEBP4-bound ATG8, resulting in lipidation of ATG8 and initiation of autophagy.

PEBP4 balances apoptosis and autophagy in viruliferous whitefly to optimize virus loading without obvious fitness cost.
Phosphoproteomics reveals new insights into the role of PknG during the persistence of pathogenic mycobacteria in host macrophages
Authors: Baros-Steyl Seanantha S. , Nakedi Kehilwe C. , Ganief Tariq A. , Okendo Javan O. , Tabb David L. , Soares Nelson C. , Blackburn Jonathan M.
Published: January 2021

Pathogenic mycobacteria, such asMycobacterium tuberculosis, modulate the host immune system to evade clearance and promote long-term persistence, resulting in disease progression or latent infection. Understanding the mechanisms pathogenic mycobacteria use to escape elimination by the host immune system is critical to better understanding the molecular mechanisms of mycobacterial infection. Protein kinase G (PknG) in pathogenic mycobacteria has been shown to play an important role in avoiding clearance by macrophages through blocking phagosome-lysosome fusion; however, the exact mechanism is not completely understood. Here, to further investigate the role of mycobacterial PknG during early events of macrophage infection, RAW 264.7 macrophage cell lines were infected withM. bovisBCG wild-type and PknG knock-out mutant strains. After proteolysis, phosphopeptides were enriched via TiO2 columns and subjected to LC-MS/MS to identify differentially phosphorylated peptides between the wild-type and PknG mutant infected macrophages. A total of 1401 phosphosites on 914 unique proteins were identified. Following phosphoproteome normalisation and differential expression analysis, a total of 149 phosphosites were differentially phosphorylated in the wild-type infected RAW 264.7 macrophages versus the PknG knock-out mutant. A subset of 95 phosphosites was differentially up-regulated in the presence of PknG. Functional analysis of our data revealed that PknG kinase activity reprograms normal macrophage function through interfering with host cytoskeletal organisation, spliceosomal machinery, translational initiation, and programmed cell death. Differentially phosphorylated proteins in this study serve as a foundation for further validation and PknG host substrate assignment.

Importance

Tuberculosis (TB) remains one of the leading causes of death from infection worldwide, due to the ability ofMycobacterium tuberculosis(Mtb) to survive and replicate within the host, establishing reservoirs of live bacteria that promote persistence and recurrence of disease. Understanding the mechanisms thatMtbuses to evade the host immune system is thus a major goal in the TB field. Protein kinase G is thought to play an important role inMtbavoiding clearance by the host through disruption of macrophage function, but the underlying molecular mechanisms of this are not well understood. Here, our new phosphoproteomic data reveals that mycobacterial PknG substantially reprograms normal macrophage function through extensive PknG-mediated post-translational control of critical host cellular processes. These novel findings therefore considerably increase our knowledge of mycobacterial pathogenicity, including specific host cellular pathways that might be re-activatable through host-directed therapy, thereby restoring macrophage ability to eliminateMtb.
Genome recombination-mediated tRNA up-regulation conducts general antibiotic resistance of bacteria at early stage
Authors: Fang Huiying , Zeng Guandi , Zhao Jing , Zheng Tingkai , Xu Lina , Gu Wei , Liu Yutong , Zhang Jinning , Sun Xuesong , Zhang Gong
Published: January 2021

Bacterial antibiotic resistance sets a great challenge to human health. It seems that the bacteria can spontaneously evolve resistance against any antibiotic within short time without the horizontal transfer of heterologous genes and before accumulating drug-resistant mutations. We have shown that the tRNA-mediated translational regulation counteracts the reactive oxygen species in bacteria. In this study, we demonstrated that isolated and subculturedEscherichia colielevated its tRNAs under antibiotic stress to rapidly provide antibiotic resistance, especially at the early stage, before upregulating the efflux pump and evolving resistance mutations. The DNA recombination system repaired the antibiotic-induced DNA breakage in the genome, causing numerous structural variations. These structural variations are overrepresented near the tRNA genes, which indicated the cause of tRNA up-regulation. The strains knocking out the recombination system could not up-regulate tRNAs, and coincidently, they could hardly evolve antibiotic resistance in multiple antibiotics, respectively. With these results, we proposed a multi-stage model of bacterial antibiotic resistance in an isolated scenario: the early stage (recombination – tRNA up-regulation – translational regulation); the medium stage (up-regulation of efflux pump); the late stage (resistance mutations). These results also indicated that the bacterial DNA recombination system and tRNA could be targeted to retard the bacterial spontaneous drug resistance.
Alcohol consumption is associated with structural changes in various organ systems: A population-based study in UK Biobank
Authors: Evangelou Evangelos , Suzuki Hideaki , Bai Wenjia , Pazoki Raha , Gao He , Matthews Paul M , Elliott Paul
Published: January 2021

Excessive alcohol consumption is associated with damage to various organs, but its multi-organ effects have not been characterised across the usual range of alcohol drinking in a large general population sample. We assessed global effects of alcohol consumption on quantitative magnetic resonance imaging phenotypic measures of the brain, heart, aorta and liver of UK-Biobank participants who reported drinking alcohol. We found a monotonic association of higher alcohol consumption with lower normalised brain volume across the range of alcohol intakes (–1.7×10−3±0.76×10−3per doubling of alcohol consumption,P=3.0×10−14). Alcohol consumption also was associated directly with measures of left ventricular mass index and left ventricular and atrial volume indices. Liver fat increased by a mean of 0.15% per doubling of alcohol consumption. Our results imply that there is not a “safe threshold” below which there are no toxic effects of alcohol. Current public health guidelines concerning alcohol consumption may need to be revisited.
Coupled myovascular expansion directs cardiac growth and regeneration
Authors: DeBenedittis Paige , Karpurapu Anish , Henry Albert , Thomas Michael C. , McCord Timothy J. , Brezitski Kyla , Prasad Anil , Kobayashi Yoshihiko , Shah Svati H. , Kontos Christopher D. , Tata Purushothama Rao , Lumbers R. Thomas , Karra Ravi
Published: January 2021

Background

Heart regeneration requires multiple cell types to enable cardiomyocyte (CM) proliferation. How these cells interact to create growth niches is unclear. Here we profile proliferation kinetics of cardiac endothelial cells (CECs) and CMs in the neonatal mouse heart and find that they are spatiotemporally coupled.

Methods and Results

We show that coupled myovascular expansion during cardiac growth or regeneration is dependent upon VEGF-VEGFR2 signaling, as genetic deletion ofVegfr2from CECs or inhibition of VEGFA abrogates both CEC and CM proliferation. Repair of cryoinjury displays poor spatial coupling of CEC and CM proliferation. Boosting CEC density after cryoinjury with virus encodingVegfaenhances regeneration. Using Mendelian randomization, we demonstrate that circulating VEGFA levels are positively linked with human myocardial mass, suggesting thatVegfacan stimulate human cardiac growth.

Conclusions

Our work demonstrates the importance of coupled CEC and CM expansion and reveals a myovascular niche that may be therapeutically targeted for heart regeneration.