bluuebunny/crossref_metadata_2025_split huggingface dataset:
High dose insulin therapy for inotropic support during veno-arterial extracorporeal membrane oxygenation decannulation: A case report
Authors: Shah Kartik R. , Przybysz Thomas M. , Ushakumari Deepu , Geib Ann-Jeannette 
Published: August 2022

Rationale:
High-dose insulin (HDI) therapy has been used as inotropic support for toxin-induced cardiogenic shock, but literature suggests that it can also be used in non-toxin-induced cardiogenic shock states. Its use has not been reported in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) decannulation.

Patient concerns:
A 56-year-old male presented with progressive dyspnea and lower extremity edema without any reported toxic ingestion.

Diagnosis:
After left heart catheterization, he was diagnosed with acute biventricular nonischemic cardiac failure that ultimately required VA-ECMO support for 8 days, after which decannulation was planned.

Interventions:
During decannulation, he was initiated on HDI therapy via a 1 U/kg regular insulin bolus with 25 g of dextrose and a 1 U/kg/hr insulin infusion.

Outcomes:
During the decannulation, he was monitored with transesophageal echocardiography. Initially, left ventricular (LV) ejection fraction (EF) was estimated at 10% to 15%. Transesophageal echocardiography after HDI but prior to decannulation showed LVEF 30% to 40%. Transthoracic echocardiography 3.5 hours after HDI bolus and decannulation revealed normal LV systolic function; LVEF 50% to 55%.

Lessons:
While multiple interventions occurred during decannulation, HDI therapy may have assisted in transitioning off ECMO support, and HDI should be investigated as an adjunctive option in future decannulations and other non-toxin-induced cardiogenic shock states.
Comparison of olecranon osteotomy and paratricipital approach in distal humerus intra-articular fracture: A systematic review and meta-analysis
Authors: Jeong Ho-Seung , Yang Jae Young , Jeon Seung Jun , Shon Hyun-Chul , Oh Jong-Keon , Lim Eic Ju 
Published: August 2022

Background:
Surgical outcomes of the paratricipital approach (PT) and olecranon osteotomy (OO) for the treatment of distal humerus intra-articular fracture have been reported. However, there is no consensus regarding which approach is better in terms of functional outcomes and complications. This study aimed to compare the operation time, functional outcomes, and complications of OO and PT.

Methods:
The databases of MEDLINE, Embase, and Cochrane Library were systematically searched for studies published before June 1, 2021. We performed synthetic analysis of the operation time, functional outcomes, and incidence of complication after the conduct of OO group or PT group in patients with distal humerus intra-articular fractures.

Results:
Five studies were included representing a total of 243 patients who underwent surgery for distal humerus intra-articular fractures. A pooled analysis showed that there was a longer operation time in the OO group compared with the PT group (mean difference [MD] = 13.32, 95% CI: 3.78–22.87; P = .006). There was no significant difference between the functional outcomes of the OO and PT groups (elbow flexion: MD = 2.4, 95% CI: −0.82 to 5.79, P = .14; elbow extension: MD = 0.36, 95% CI: −2.20 to 2.92, P = .78; elbow arc of motion: MD = 0.40, 95% CI: −4.05 to 4.84, P = .86; Mayo Elbow Performance score: MD = −1.37, 95% CI: −4.73 to 1.98, P = .42). The incidence of infection was significantly higher in the OO group compared with that of the PT group (odds ratio [OR] = 3.82, 95% CI: 1.03–14.16, P = .04). There was no significant difference between the 2 groups in terms of the heterotopic ossification and ulnar neuropathy (OR = 1.85, 95% CI: 0.51–6.71, P = .35 and OR = 2.74, 95% CI: 0.60–12.48, P = .19, respectively).

Conclusions:
Since the choice of surgical approach does not influence outcomes, surgeons can base their choice of approach on the basis of their own experience and familiarity with the procedure and the need to visualize the entire articular surface in complex intra-articular fracture patterns.
Microsatellite instability/mismatch repair deficiency and activation of the Wnt/β-catenin signaling pathway in gastric adenocarcinoma of the fundic gland: A case report
Authors: Yang Guang 
Published: August 2022

Rationale:
Gastric adenocarcinoma of the fundic gland is a rare, well-differentiated variant of gastric adenocarcinoma, which has been proposed as a novel disease entity. As a result of mismatch repair deficiency, microsatellite instability has been frequently observed in various human cancers and widely performed in the area of cancer pathogenesis. Herein, we report a case of gastric adenocarcinoma of fundic gland presented with microsatellite instability phenotype.

Patient concerns:
A 46-year-old man was referred to our hospital for abdominal distension and pain.

Diagnosis:
The patient contained 3 tumor lesions with different degrees of histologic differentiation and microsatellite instability. The lesions were located in the upper third of the stomach. The tumor size was 55 mm. Macroscopically, tumor showed an ulcerative type. In terms of depth of invasion, tumor lesion invaded into subserosa with lymphatic invasion. In addition, this patient did not present GNAS mutation but harbored AXIN2 mutation. By immunohistochemistry, the expression level of β-catenin protein in the nucleus of the carcinoma cells was obviously higher than that in normal nucleus. Compared with microsatellite instability-low lesion, PD-1, PD-L1, and CD8 were positive in the microsatellite instability-high lesions.

Interventions:
The patient underwent surgical resection and postoperative chemotherapy.

Outcomes:
The patient experienced distant metastasis and died from severe complications after 6 months of treatment.

Lessons:
These results suggested that the mutation of Wnt component genes associated with Wnt/β-catenin signaling pathway activation may play a role in promoting the occurrence of gastric adenocarcinoma of fundic gland. This is the first report of a gastric adenocarcinoma of fundic gland with microsatellite instability. These findings modify our understanding of the pathophysiology of gastric adenocarcinoma of fundic gland.
Thyroid storm complicated by corpus callosum infarction in a young patient: A case report and literature review
Authors: Cai Yunjia , Ren Linan , Liu Xinming , Li Chen , Gang Xiaokun , Wang Guixia 
Published: August 2022

Rationale:
Thyroid storm (TS) is a rare life-threatening hypermetabolic thyrotoxicosis with an incidence of 0.57–0.76/100,000. The coexistence of TS and acute cerebral infarction is rare. Previous studies have shown that hyperthyroidism complicated by cerebral infarction mainly occurs in the intracranial basal ganglia; however, there are no reports of corpus callosum infarction. We report a case of TS complicated by cerebral infarction of the corpus callosum at our hospital.

Patient concerns:
A 31-year-old male patient with a history of hyperthyroidism was admitted to the hospital because of fatigue, palpitations, fever, and profuse sweating accompanied by a mild decrease in the muscle strength of the left limb. Diagnosis of a TS was confirmed by the laboratory test results. The patient’s clinical symptoms gradually improved after treatment. However, his left limb muscle strength progressively decreased, and the bilateral pathological signs were positive at the same time. Magnetic resonance imaging (MRI) of the head revealed acute cerebral infarction of the corpus callosum and pons.

Diagnosis:
The diagnosis was thyroid strom with acute cerebral infarction of the corpus callosum and pons and severe stenosis or occlusion of the basilar artery.

Interventions:
The patient was given 300 mg hydrocortisone intravenously per day, propylthiouracil tablets of 200 mg 3 times a day by nasal feeding, and 20 mg propranolol three times a day by nasal feeding. Aspirin and clopidogrel were administered to prevent platelet aggregation, and atorvastatin calcium was administered to lower lipid levels to stabilize plaques.

Outcomes:
The patient’s left limb muscle strength recovered to grade 4+, and he could walk beside the bed with support. Simultaneously, thyroid function was better than before.

Lessons:
Careful physical examination should be performed in patients with thyroid storm, and head imaging examination should be improved for the early detection of cerebral infarction.
Effects of nutritional supplement and resistance training for sarcopenia in patients with inflammatory bowel disease: A randomized controlled trial
Authors: Zhao Jiaxi , Huang Yiqin , Yu Xiaofeng 
Published: August 2022

Background:
Nutritional supplementation and resistance training are broadly recommended as part of the treatment of sarcopenia, but studies that have evaluated interventions in inflammatory bowel disease patients with sarcopenia are lacking. The aim of this study was to evaluate the effects of nutritional supplementation and resistance training for improving height-adjusted appendicular skeletal muscle mass (ASM/H2) and medical indices in patients with inflammatory bowel disease.

Methods:
This randomized, double-blind, placebo-controlled trial of forty-five participants was performed at Huadong Hospital Affiliated to Fudan University in Shanghai from September 2020 to June 2021. Eligible participants were randomly assigned to receive whey protein (10 g/d) or placebo (10 g/d) for 8 weeks while completing a resistance training program (3 times a week). Data such as ASM/H2 and other medical indices were collected at baseline and at 4 and 8 weeks of intervention.

Results:
Fifteen participants were allocated to the resistance training and whey protein (RT+WP) group, and thirteen participants were allocated to the resistance training and placebo (RT+placebo) group. The ASM/H2 significantly increased in the RT+WP group after 4 and 8 weeks of intervention, and the ASM/H2 of the RT+WP group was significantly higher than that of the RT+placebo group after 4 and 8 weeks of intervention (F = 1.092, P = .035). Both interventions significantly increased albumin (F = 7.214, P = .003). Hemoglobin and creatinine significantly increased in the RT+WP group (F = 3.592, P = .035; F = 3.922, P = .033, respectively). In addition, a significant group × time interaction was not observed for body mass index, 5-time chair stand test time, 3-metre walk speed, grip strength, waist circumference, hip circumference, or waist-to-hip ratio (P > .05).

Conclusions:
Nutritional supplementation may be effective in improving sarcopenia, as well as many other physiological indicators during resistance training.
People With Functional Disability and Access to Health Care During the COVID-19 Pandemic
Authors: Xie Zhigang , Hong Young-Rock , Tanner Rebecca , Marlow Nicole M. 
Published: August 2022

Introduction:
The COVID-19 pandemic and nationwide restriction measures have disrupted health care delivery and access for the general population. There is limited evidence about access to care issues (delayed and forgone care) due to the pandemic among people with disability (PWD).

Methods:
This study used the 2020 National Health Interview Survey data. Disability status was defined by disability severity (moderate and severe disability), type, and the number of disabling limitations. Descriptive analysis and multivariate logistic regression (adjusted for sociodemographic and health-related characteristics) were conducted to estimate delayed/forgone care (yes/no) between PWD and people without disability (PWoD).

Results:
Among 17,528 US adults, 40.7% reported living with disability. A higher proportion of respondents with severe and moderate disability reported delaying care than PWoD (severe=33.2%; moderate=27.5%; PWoD=20.0%, P<0.001). The same was true for forgone medical care (severe=26.6%; moderate=19.0%; PWoD=12.2%, P<0.001). Respondents with a moderate disability {delayed [odds ratio (OR)=1.33, 95% confidence interval (CI)=1.19, 1.49]; forgone [OR=1.46, 95% CI=1.28, 1.67]} and a severe disability [delayed (OR=1.52, 95% CI=1.27, 1.83); forgone (OR=1.84, 95% CI=1.49, 2.27)] were more likely to report delayed medical care and forgone medical care compared with PWoD. These findings were consistent across the models using disability type and the number of limitations.

Conclusions:
PWD were more likely to experience COVID-19-related delays in or forgone medical care compared with PWoD. The more severe and higher frequency of disabling limitations were associated with higher degrees of delayed and forgone medical care. Policymakers need to develop disability-inclusive responses to public health emergencies and postpandemic care provision among PWD.
SARS-CoV-2 With Concurrent Respiratory Viral Infection as a Risk Factor for a Higher Level of Care in Hospitalized Pediatric Patients
Authors: Dikranian Lea , Barry Suzanne , Ata Ashar , Chiotos Katie , Gist Katja , Bhalala Utpal , Danesh Valerie , Heavner Smitty , Gharpure Varsha , Bjornstad Erica C. , Irby Olivia , Heneghan Julia A. , Montgomery Vicki , Gupta Neha , Miller Aaron , Walkey Allan , Tripathi Sandeep , Boman Karen , Bansal Vikas , Kumar Vishakha , Kashyap Rahul , Sayed Imran , Woll Christopher ,   From the Society of Critical Care Medicine Discovery Viral Infection and Respiratory Illness Universal Study: COVID-19 Registry Investigator Group
Published: August 2022

Objective
As of early 2021, there have been over 3.5 million pediatric cases of SARS-CoV-2, including 292 pediatric deaths in the United States. Although most pediatric patients present with mild disease, they are still at risk for developing significant morbidity requiring hospitalization and intensive care unit (ICU) level of care. This study was performed to evaluate if the presence of concurrent respiratory viral infections in pediatric patients admitted to the hospital with SARS-CoV-2 was associated with an increased rate of ICU level of care.

Design
A multicenter, international, noninterventional, cross-sectional study using data provided through The Society of Critical Care Medicine Discovery Network Viral Infection and Respiratory Illness Universal Study database.

Setting
The medical ward and ICU of 67 participating hospitals.

Patients
Pediatric patients younger than 18 years hospitalized with SARS-CoV-2.

Interventions
None.

Measurements and Main Results
A total of 922 patients were included. Among these patients, 391 required ICU level care and 31 had concurrent non–SARS-CoV-2 viral coinfection. In a multivariate analysis, after accounting for age, positive blood culture, positive sputum culture, preexisting chronic medical conditions, the presence of a viral respiratory coinfection was associated with need for ICU care (odds ratio, 3.6; 95% confidence interval, 1.6–9.4; P < 0.01).

Conclusions
This study demonstrates an association between concurrent SARS-CoV-2 infection with viral respiratory coinfection and the need for ICU care. Further research is needed to identify other risk factors that can be used to derive and validate a risk-stratification tool for disease severity in pediatric patients with SARS-CoV-2.
GPR183 targets lung-resident CD301b+ conventional dendritic cells type 2 to a subtissular TSLP – TSLP receptor mediated survival niche within the adventital cuff
Authors: Zhang L. , Yu J. , Spath S. , Sheoran S. , Bejarano D , Vandestienne M , Weier AK , Quast T. , Ibrahim M. , Reimer S , Uderhardt S , Mass E. , Hasenauer J. , Pfeifer A. , Kiermaier E. , Kolanus W. , Ziegler S. , Schlitzer A. 
Published: August 2022

SummaryConventional dendritic cells (cDCs) are strategically localized throughout non-lymphoid tissues. How such spatially regulated subtissular placement is achieved remains largely elusive. Here, we reveal that GPR183 targets CD301b+ cDC2 to a TSLP-dependent survival niche within the adventital cuff. We identified a close association of CD301b+ cDC2 with PDGFRα+ fibroblasts within the adventitial region of the lung. Genetic ablation of GPR183 within the cDC lineage leads to a selective loss of CD301b+ cDC2 in conjunction with the loss of CD301b+ cDC2 : fibroblast colocalization. Next bone marrow chimeric experiments and expression studies suggested adventitial fibroblasts as the main source of 7α,25 hydroxycholesterol, the natural ligand of GPR183. Single cell transcriptomic receptor ligand inference and subsequent genetic validation revealed TSLP receptor signalling as a crucial fibroblast derived CD301b+ cDC2 survival factor. These data expose a subtissular localization mechanism for tissue-specific functionalization of CD301b+ cDC2.
The interplay between metabolic stochasticity and regulation in singleE. colicells
Authors: Wehrens Martijn , Krah Laurens H.J. , Towbin Benjamin D. , Hermsen Rutger , Tans Sander J. 
Published: August 2022

AbstractMetabolism is inherently stochastic at the cellular level. Whether cells actively regulate processes in response to these random internal variations is a fundamental problem that remains unaddressed, yet critical to understanding biological homeostasis. Here, we show that in E. coli cells, expression of the main catabolic enzymes is continuously adjusted in response to metabolic fluctuations under constant external conditions. This noise feedback is performed by the cAMP-CRP system, which controls transcription of the catabolic enzymes by modulating concentrations of the second messenger cAMP upon changes in metabolite abundance. Using time-lapse microscopy, genetic constructs that selectively disable cAMP-CRP noise feedback, and mathematical modelling, we show how fluctuations circulate through this hybrid metabolic-genetic network at sub cell-cycle timescales. This circulation of stochastic fluctuations is explained by four distinct noise propagation modes, one of which describes the continuous cAMP-CRP regulation. The model successfully predicts how noise circulation is impacted by C-sector under and over-expression. The results raise the question whether the cAMP-CRP system, as well as other metabolic regulation mechanisms, have evolved to manage internal metabolic fluctuations in addition to external growth conditions. We conjecture that second messengers may broadly function to control metabolic stochasticity and achieve cellular homeostasis.
ALK signaling drives tumorigenicity and chemoresistance of pancreatic ductal adenocarcinoma cells
Authors: Parejo-Alonso Beatriz , Royo-García Alba , Espiau-Romera Pilar , Courtois Sarah , Curiel-García Álvaro , Zagorac Sladjana , Villaoslada Isabel , Olive Kenneth P. , Heeschen Christopher , Sancho Patricia 
Published: August 2022

ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is an extremely aggressive disease characterized by its metastatic potential and chemoresistance. These traits are partially attributable to the highly tumorigenic pancreatic cancer stem cells (PaCSCs). Interestingly, these cells show unique features in order to sustain their identity and functionality, some of them amenable for therapeutic intervention. Screening of phospho-receptor tyrosine kinases revealed that PaCSCs harbored increased activation of anaplastic lymphoma kinase (ALK). We subsequently demonstrated that oncogenic ALK signaling drives tumorigenicity in PDAC patient-derived xenografts (PDXs) by promoting stemness through ligand-dependent activation. Indeed, the ALK ligands midkine (MDK) or pleiotrophin (PTN) increased self-renewal, clonogenicity and CSC frequency in several in vitro local and metastatic PDX models. Conversely, treatment with the clinically-approved ALK inhibitors Crizotinib and Ensartinib decreased CSC content and functionality in vitro and in vivo, by inducing cell death. Strikingly, ALK inhibitors sensitized chemoresistant PaCSCs to Gemcitabine, as the most used chemotherapeutic agent for PDAC treatment. Consequently, ALK inhibition delayed tumor relapse after chemotherapy in vivo by effectively decreasing the content of PaCSCs. In summary, our results demonstrate that targeting the MDK/PTN-ALK axis with clinically-approved inhibitors impairs in vivo tumorigenicity and chemoresistance in PDAC suggesting a new treatment approach to improve the long-term survival of PDAC patients.GRAPHICAL ABSTRACT
HUWE1 controls tristetraprolin proteasomal degradation by regulating its phosphorylation
Authors: Scinicariello Sara , Söderholm Adrian , Schäfer Markus , Shulkina Alexandra , Schwartz Irene , Hacker Kathrin , Gogova Rebeca , Kalis Robert Wolfgang , Froussios Kimon , Budroni Valentina , Bestehorn Annika , Clausen Tim , Kovarik Pavel , Zuber Johannes , Versteeg Gijs A. 
Published: August 2022

AbstractTristetraprolin (TTP) is a critical negative immune regulator. It binds AU-rich elements in the untranslated-regions of many mRNAs encoding pro-inflammatory mediators, thereby accelerating their decay. A key but poorly understood mechanism of TTP regulation is its timely proteolytic removal: TTP is degraded by the proteasome through yet unidentified phosphorylation-controlled drivers. In this study, we set out to identify factors controlling TTP stability. Cellular assays showed that TTP is strongly lysine-ubiquitinated, which is required for its turnover. A genetic screen identified the ubiquitin E3 ligase HUWE1 as a strong regulator of TTP proteasomal degradation, which we found to control TTP stability indirectly by regulating its phosphorylation. Pharmacological assessment of multiple kinases revealed that HUWE1-regulated TTP phosphorylation and stability was independent of the previously characterized effects of MAPK-mediated S52/S178 phosphorylation. HUWE1 function was dependent on phosphatase and E3 ligase binding sites identified in the TTP C-terminus. Our findings indicate that while phosphorylation of S52/S178 is critical for TTP stabilization at earlier times after pro-inflammatory stimulation, phosphorylation of the TTP C-terminus controls its stability at later stages.
Genetic variance and indirect genetic effects for affiliative social behavior in a wild primate
Authors: McLean Emily M. , Moorad Jacob A. , Tung Jenny , Archie Elizabeth A. , Alberts Susan C. 
Published: August 2022

ABSTRACTAffiliative social behaviors are linked to fitness components in multiple species. However, the role of genetic variance in shaping affiliative social behaviors remains largely unknown, limiting our understanding of how these behaviors can respond to natural selection. Here, we employed the ‘animal model’ to estimate both environmental and genetic sources of variance and covariance in grooming behavior in the well-studied Amboseli baboon population in Kenya. We found that grooming given, grooming received, and total grooming all are similarly heritable (h2=0.22, h2=0.16, and h2=0.26 respectively), and that rank and the presence of kin contribute to environmental variance. We detected small but measurable indirect genetic effects of partner identity on the amount of grooming given within dyadic grooming partnerships. The genetic correlation between grooming given and grooming received was exceptionally strong and positive (R=0.94 ± 0.12), and the indirect and direct genetic effects for grooming given were also strongly positively correlated (R=0.86 ± 0.06). Our results provide insight into the evolvability of affiliative behavior in wild animals, including the possibility for correlations between direct and indirect genetic effects to accelerate the response to selection. As such they provide novel information about the genetic architecture of social behavior in nature, with important implications for the evolution of cooperation and reciprocity.