Miracle-dz/UniFAR-FTUs huggingface dataset:
Low‐dose desoxycorticosterone pivalate treatment of hypoadrenocorticism in dogs: A randomized controlled clinical trial

Abstract Background Desoxycorticosterone pivalate (DOCP) is a commonly used mineralocorticoid replacement for dogs with primary hypoadrenocorticism (HA), but manufacturer‐recommended dosing protocols can be cost‐prohibitive. Recent reports also have raised concerns that label dose protocols could be excessive. Objective To investigate the relative efficacy and adverse effects of 2 DOCP dosages in dogs with primary glucocorticoid and mineralocorticoid deficient HA. Animals Thirty‐seven dogs, including 19 test population dogs and 18 controls. Methods Randomized controlled double‐blinded clinical trial. Dogs with newly diagnosed primary HA were assigned to standard (2.2 mg/kg q30d, control population) or low‐dose (1.1 mg/kg q30d, test population) DOCP treatment. Clinical and laboratory variables were assessed 10 to 14 days and approximately 30 days after each DOCP treatment for 90 days. Results Mean serum sodium to potassium ratios at reevaluations were ≥32 in both populations throughout the study. No dog developed electrolyte abnormalities warranting medical treatment, although hypokalemia occurred on at least 1 occasion in 9 controls and 6 test population dogs. Urine specific gravities (median, interquartile range) were lower in control dogs (1.022, 1.016‐1.029) as compared to test population dogs (1.033, 1.023‐1.039; P = .006). Plasma renin activity was overly suppressed on 84 of 104 (80.8%) assessments in control dogs whereas increased renin activity occurred on 23 of 112 (20.5%) assessments in test population dogs. Conclusions and Clinical Importance Low‐dose DOCP protocols appear to be safe and effective for treatment of HA in most dogs. Standard‐dose protocols are more likely to result in biochemical evidence of overtreatment.
A massive rock and ice avalanche caused the 2021 disaster at Chamoli, Indian Himalaya

A deadly cascade A catastrophic landslide in Uttarakhand state in India on February 2021 damaged two hydropower plants, and more than 200 people were killed or are missing. Shugar et al. describe the cascade of events that led to this disaster. A massive rock and ice avalanche roared down a Himalayan valley, turning into a deadly debris flow upstream from the first of the two hydropower plants. The sequence of events highlights the increasing risk in the Himalayas caused by increased warming and development. Science, abh4455, this issue p. 300 A cascade of events starting with a massive avalanche eventually triggered a deadly debris flow in the Indian Himalaya. On 7 February 2021, a catastrophic mass flow descended the Ronti Gad, Rishiganga, and Dhauliganga valleys in Chamoli, Uttarakhand, India, causing widespread devastation and severely damaging two hydropower projects. More than 200 people were killed or are missing. Our analysis of satellite imagery, seismic records, numerical model results, and eyewitness videos reveals that ~27 × 106 cubic meters of rock and glacier ice collapsed from the steep north face of Ronti Peak. The rock and ice avalanche rapidly transformed into an extraordinarily large and mobile debris flow that transported boulders greater than 20 meters in diameter and scoured the valley walls up to 220 meters above the valley floor. The intersection of the hazard cascade with downvalley infrastructure resulted in a disaster, which highlights key questions about adequate monitoring and sustainable development in the Himalaya as well as other remote, high-mountain environments.
Evolution of CT findings after anticoagulant treatment for acute pulmonary embolism in patients with and without an ultimate diagnosis of chronic thromboembolic pulmonary hypertension

Introduction The pulmonary arterial morphology of patients with pulmonary embolism (PE) is diverse and it is unclear how the different vascular lesions evolve after initiation of anticoagulant treatment. A better understanding of the evolution of computed tomography pulmonary angiography (CTPA) findings after the start of anticoagulant treatment may help to better identify those PE patients prone to develop chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to assess the evolution of various thromboembolic lesions on CTPA over time after the initiation of adequate anticoagulant treatment in individual acute PE patients with and without an ultimate diagnosis of CTEPH. Methods We analysed CTPA at diagnosis of acute PE (baseline) and at follow-up in 41 patients with CTEPH and 124 patients without an ultimate diagnosis of CTEPH, all receiving anticoagulant treatment. Central and segmental pulmonary arteries were scored by expert chest radiologists as normal or affected. Lesions were further subclassified as 1) central thrombus, 2) total thrombotic occlusion, 3) mural thrombus, 4) web or 5) tapered pulmonary artery. Results Central thrombi resolved after anticoagulant treatment, while mural thrombi and total thrombotic occlusions either resolved or evolved into webs or tapered pulmonary arteries. Only patients with an ultimate diagnosis of CTEPH exhibited webs and tapered pulmonary arteries on the baseline scan. Moreover, such lesions always persisted after follow-up. Conclusions Webs and tapered pulmonary arteries at the time of PE diagnosis strongly indicate a state of chronic PE and should raise awareness for possible CTEPH, particularly in patients with persistent dyspnoea after anticoagulant treatment for acute PE. Webs and tapered pulmonary arteries at the time of PE diagnosis strongly indicate a state of chronic PE and should raise awareness for possible CTEPH, particularly in patients with persistent dyspnoea after anticoagulant treatment for acute PE https://bit.ly/3f0R2jP
“(I Think) My Mother Thinks I Am, Therefore I Am.” The Looking-glass Self in Maltreated Children and Adolescents

Children and adolescents with maltreatment experiences show worse representations of themselves, as compared to their nonmaltreated counterparts. According to the looking-glass self hypothesis (LGSH), individuals’ self-representations (SR) stem from interactions with significant others, reflecting associations between what significant others think of them (i.e., actual appraisals), individuals’ perceptions of significant others’ appraisals of them (i.e., reflected appraisals), and SR. However, little is known about the looking-glass self process in maltreated children and adolescents. This multi-informant study aimed to test the LGSH within the mother–child relationship with children and adolescents with maltreatment experiences. Specifically, including maltreatment experiences as co-predictors, this study analyzed the mediating role of mothers’ reflected appraisals (MRA) in associations between mothers’ actual appraisals (MAA) and children/adolescents’ SR. Participants were 203 children/adolescents (52.5% boys), 8–16 years old (M = 12.6; SD = 2.49), assisted by children and youth protection committees (CYPC), their mother, and their CYPC case workers. Case workers reported on child/adolescent maltreatment, children/adolescents reported on SR and MRA, and mothers reported on MAA. A multiple mediation path analysis revealed significant mediation effects of MRA between MAA and child/adolescent SR in instrumental, social, emotional, intelligence, and opposition SR, thus supporting the LGSH in the context of child/adolescent maltreatment. Also, psychological neglect was associated to worse intelligence SR, mediated by intelligence reflected appraisals. Findings emphasize the importance of the role of MRA on maltreated children and adolescents’ SR construction process, and provide useful clues to incorporate in prevention and intervention strategies targeting maltreated children and adolescents.
Clonal Dynamics and clinical implications of Post-Remission Clonal Hematopoiesis in Acute Myeloid Leukemia (AML).

While clonal hematopoiesis (CH) can precede the development of acute myeloid leukemia (AML), it can also persist after achieving remission. Long-term clonal dynamics and clinical implications of persistent CH are not well understood. Here, we studied the prevalence, dynamics and clinical implications of post-remission CH in 164 AML patients who attained complete remission after induction chemotherapies. Post-remission CH was identified in 79 (49%) patients. Post-remission CH persisted long-term in 91% of the trackable patients despite treatment with various types of consolidation and maintenance therapies. Post-remission CH was eradicated in 20 out of 21 (95%) patients who underwent allogeneic stem cell transplant. While patients with post-remission CH as a group had comparable hematopoiesis with those without it, patients with persistent TET2 mutations showed significant neutropenia long-term. Post-remission CH had little impact on relapse risk, non-relapse mortality, and incidence of atherosclerotic cardiovascular disease, although the clinical impact of post-CR CH was heterogeneous among different mutations. These data suggest that while residual clonal hematopoietic stem cells (HSCs) are generally resistant to consolidation and maintenance therapies, they retain the ability to maintain normal hematopoiesis and have little impact on clinical outcomes, although larger study is needed to dissect the gene-specific heterogeneity.
Effect of taurolidine citrate and unfractionated heparin on inflammatory state and dialysis adequacy in hemodialysis patients

Background and aim: HD patients using dialysis catheters have been associated with chronic inflammatory state. In Egypt 6.6% of HD patients use catheters, of which short term catheters represent 59.6% and 40.4% with long-term catheters. In this study, we aimed to assess the effect of Taurolidine citrate and unfractionated heparin combination (Taurolock-hep500™) as a lock solution compared to unfractionated heparin alone on inflammatory markers, incidence of catheter related blood stream infections (CRBSI) and dialysis adequacy in HD patients with temporary HD catheters only, for 4 weeks duration. Methods: Sixty ESRD patients from hemodialysis units in Ain-Shams University hospitals (ASUH) at the time of catheter insertion we enrolled in our study. They were randomized into two groups: Group 1: Thirty patients received Taurolock-hep500™ as a catheter lock solution at the end of each hemodialysis session. Group 2: Thirty patients received unfractionated heparin as a catheter lock solution. hsCRP and IL-6 were measured at baseline and 1 month after using the lock solutions. Blood cultures were done in patients who developed symptoms of catheter related infections. Results: At the end of the study, Inflammatory markers were significantly higher in group 2 (p-value: 0.045, 0.001, and 0.018 for WBCs, hsCRP and IL-6, respectively). Group 1 had better dialysis adequacy assessed by URR (p-value: 0.007 and 0.001, respectively). CRBSI were demonstrated in nine patients in group 2 (30%) in contrast to one patient only in group 1(3.3%) (p-value: 0.006) with pseudomonas being the most common isolated organism (27.7%). Conclusion: Use of (Taurolock-hep500™) for temporary hemodialysis catheters was associated with lower levels of inflammation markers and lower incidence of CRBSI and better catheter performance.
Pyrotinib Treatment in Patients With HER2-positive Metastatic Breast Cancer and Brain Metastasis: Exploratory Final Analysis of Real-World, Multicenter Data

Purpose: Patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have poor prognoses. Pyrotinib has shown promising antitumor activity in MBC to improve progression-free survival (PFS). However, findings based on real-world data to analyze whether pyrotinib affects overall survival (OS) remain scarce. Experimental Design: This real-world study is an exploratory analysis of brain metastasis (BM) and the final update of our preceding study of 168 patients with HER2+ MBC. PFS, OS, tumor mutation burden (TMB), clinical benefit rate (CBR), and overall response rate (ORR) were analyzed. Results: Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants. High TMB was associated with poor OS (P = 0.0072) and PFS (P = 0.0028). In the 39 patients with BM, the median PFS and OS were 8.67 and 13.93 months, respectively. The surgery/radiation (S/R) group of patients with BM had prolonged survival (PFS: 9.97 vs. 7.73 months P = 0.19; OS: 20.67 vs. 12.43 months P = 0.021) compared with the no surgery/no radiation group (NS/NR). The CBR was 58.6% (S/R) vs. 41.4% (NS/NR), while the ORR was 24.1% (S/R) vs. 31.0% (NS/NR). Conclusions: Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort. TMB could be an exploratory biomarker for predicting PFS and OS, but its clinical application still needs further verification.
The Content of Nostalgic Memories Among People Living with Dementia

Although dementia may affect the reliability of autobiographical memories, the psychological properties of nostalgic memories may be preserved. We compared the content of nostalgic (n = 36) and ordinary (n = 31) narratives of 67 participants living with dementia. Narratives were rated according to their self-oriented, social, and existential properties, as well as their affective content. Social properties and affective content were assessed using a linguistic word count procedure. Compared to the ordinary narratives described in the control condition, nostalgic narratives described a typical events, expressed more positive affect, and had more expressions of self-esteem and self-continuity. They were also rated higher on companionship, connectedness and the closeness of relationships, and reflected life as being meaningful. Despite their cognitive impairment, people living with dementia experience nostalgia in similar ways to cognitively healthy adults, with their nostalgic narratives containing self-oriented, social, and existential properties.
Maternal and fetal outcomes associated with infective endocarditis in pregnancy.

INTRODUCTION Infective endocarditis (IE) is a rare but serious infection complicating pregnancy. Little is known about IE management and outcomes in this population. METHODS The National Readmissions Database was used to obtain data between October 2015 and October 2018. Billing codes identified admissions for IE in female patients of reproductive age. Demographic characteristics, comorbidities, and outcomes were compared between a) patients with maternity-associated and non-maternity associated IE, and b) obstetric patients who delivered with and without IE. Weighted regressions were used to examine outcomes in adjusted models. RESULTS We identified 12,602 reproductive-aged female patients with a diagnosis of IE, of which 382 (weighted national estimate: 748) were maternity-associated. Of these cases, 117 (weighted national estimate: 217) occurred during a delivery admission. Compared to patients with non-maternity-associated IE, maternity-associated infection was associated with younger age (mean 29.0 vs. 36.6 years, P < 0.001), Medicaid coverage (72.5% vs. 47.2%, P < 0.001), and drug use (76.2% vs. 59.8%, P < 0.001). Mortality was comparable (8.1% vs. 10.6%, aRR = 1.03, 95% CI 0.71-1.48). Compared to patients delivering without IE, IE complicating delivery was associated with worse maternal and fetal outcomes, including maternal mortality (17.2% vs. <0.01%, aRR = 323.32, 95% CI 127.74-818.37) and preterm birth (55.7% vs. 10.1%, aRR = 3.61, 95% CI 2.58-5.08). CONCLUSION Maternity-associated IE does not appear to confer additional risk for adverse outcome over non-maternity-associated infection. Patients delivering with IE have worse maternal and fetal outcomes than those whose deliveries are not complicated by IE.
A comparative study on perinatal outcomes of red blood cell–alloimmunized pregnancies with anti‐RhD in combination and anti‐RhD alone in China

The advent of intrauterine transfusion (IUT) has improved the survival of severe foetal anaemia. The aim of this study was to compare the perinatal outcomes of red blood cell (RBC)–alloimmunized pregnancies with anti‐RhD in combination and anti‐RhD alone in China.
Decreases in COVID-19 Cases, Emergency Department Visits, Hospital Admissions, and Deaths Among Older Adults Following the Introduction of COVID-19 Vaccine — United States, September 6, 2020–May 1, 2021

Throughout the COVID-19 pandemic, older U.S. adults have been at increased risk for severe COVID-19-associated illness and death (1). On December 14, 2020, the United States began a nationwide vaccination campaign after the Food and Drug Administration's Emergency Use Authorization of Pfizer-BioNTech COVID-19 vaccine. The Advisory Committee on Immunization Practices (ACIP) recommended prioritizing health care personnel and residents of long-term care facilities, followed by essential workers and persons at risk for severe illness, including adults aged ≥65 years, in the early phases of the vaccination program (2). By May 1, 2021, 82%, 63%, and 42% of persons aged ≥65, 50-64, and 18-49 years, respectively, had received ≥1 COVID-19 vaccine dose. CDC calculated the rates of COVID-19 cases, emergency department (ED) visits, hospital admissions, and deaths by age group during November 29-December 12, 2020 (prevaccine) and April 18-May 1, 2021. The rate ratios comparing the oldest age groups (≥70 years for hospital admissions; ≥65 years for other measures) with adults aged 18-49 years were 40%, 59%, 65%, and 66% lower, respectively, in the latter period. These differential declines are likely due, in part, to higher COVID-19 vaccination coverage among older adults, highlighting the potential benefits of rapidly increasing vaccination coverage.
Predicting overall survival and resection in patients with locally advanced pancreatic cancer treated with FOLFIRINOX: Development and internal validation of two nomograms

Patients with locally advanced pancreatic cancer (LAPC) are increasingly treated with FOLFIRINOX, resulting in improved survival and resection of tumors that were initially unresectable. It remains unclear, however, which specific patients benefit from FOLFIRINOX. Two nomograms were developed predicting overall survival (OS) and resection at the start of FOLFIRINOX for LAPC.
External Validation Confirms Validity of a Simple Model to Predict Bowel Outcome After Traumatic Spinal Cord Injury

Background. The prediction of functional outcomes after spinal cord injury (SCI) is essential to plan the rehabilitation phase and the social reintegration. Recently, 2 models to predict independent and reliable bowel management 1 year after traumatic SCI have been derived and validated in 2 cohorts of patients included in the European Multicenter Study about Spinal Cord Injury (EMSCI). Objective. We aimed to validate 2 prediction models for bowel outcome after traumatic SCI in a patient sample external to EMSCI. Methods. The simplified model (based on a single predictor, the International Standards for Neurological Classification of Spinal Cord Injury [ISNCSCI] total motor score) and the full model (based on 2 predictors, the ISNCSCI total motor score and item 3a of the Spinal Cord Independence Measure) were applied to the retrospectively collected data of 111 patients with traumatic SCI. Results. The simplified and the full models showed excellent discrimination with an area under the receiver operating characteristic curve of . 939 (95% confidence interval (CI) . 87-1.00) and . 922 (95% CI 0.85-.99), respectively. Both models displayed similar results for sensitivity and negative predictive values; however, the simplified model showed higher values for specificity, positive predictive values, and accuracy. The calibration analysis showed a partial overlap between predicted probabilities and observed proportion, with better and acceptable calibration for the simplified model. Conclusions. Using an independent sample, our study demonstrates the validity of a simple model to predict independent and reliable bowel management 1 year after traumatic SCI.
Bio-instructive hydrogel expands the paracrine potency of mesenchymal stem cells

The therapeutic efficacy of clinically applied mesenchymal stromal cells (MSCs) is limited due to their injection into harsh in vivo environments, resulting in the significant loss of their secretory function upon transplantation. A potential strategy for preserving their full therapeutic potential is encapsulation of MSCs in a specialized protective microenvironment, for example hydrogels. However, commonly used injectable hydrogels for cell delivery fail to provide the bio-instructive cues needed to sustain and stimulate cellular therapeutic functions. Here we introduce a customizable collagen I-hyaluronic acid (COL-HA)-based hydrogel platform for the encapsulation of MSCs. Cells encapsulated within COL-HA showed a significant expansion of their secretory profile compared to MSCs cultured in standard (2D) cell culture dishes or encapsulated in other hydrogels. Functionalization of the COL-HA backbone with thiol-modified glycoproteins such as laminin led to further changes in the paracrine profile of MSCs. In depth profiling of more than 250 proteins revealed an expanded secretion profile of proangiogenic, neuroprotective and immunomodulatory paracrine factors in COL-HA-encapsulated MSCs with a predicted augmented pro-angiogenic potential. This was confirmed by increased capillary network formation of endothelial cells stimulated by conditioned media from COL-HA-encapsulated MSCs. Our findings suggest that encapsulation of therapeutic cells in a protective COL-HA hydrogel layer provides the necessary bio-instructive cues to maintain and direct their therapeutic potential. Our customizable hydrogel combines bioactivity and clinically applicable properties such as injectability, on-demand polymerization and tissue-specific elasticity, all features that will support and improve the ability to successfully deliver functional MSCs into patients.
Single-cell transcriptome profiling of thyroid hormone effectors in the human fetal neocortex: expression of SLCO1C1, DIO2, and THRB in specific cell types.

BACKGROUND Thyroid hormones are crucial for brain development, acting through the thyroid hormone nuclear receptors (TR) α1 and β to control gene expression. T3, the receptor-ligand, is transported into the brain from the blood by the monocarboxylate transporter 8 (MCT8). Another source of brain T3 is from the local deiodination of T4 by type 2 deiodinase (DIO2). While these mechanisms are very similar in mice and humans, important species-specific differences confound our understanding of disease using mouse models. To fill this knowledge gap on thyroid hormone action in the human fetal brain, we analyzed the expression of transporters, DIO2, and TRs, which we call thyroid hormone effectors, at single-cell resolution. METHODS We analyzed publicly available single-cell transcriptome datasets of isolated cerebral cortex neural cells from three different studies, with expression data from 393 to almost 40,000 cells. We generated Uniform Manifold Approximation and Projection scatterplots and cell clusters to identify differentially expressed genes between clusters, and correlated their gene signatures with the expression of thyroid effectors. RESULTS The radial glia, mainly the outer radial glia, and astrocytes coexpress SLCO1C1 and DIO2, indicating close cooperation between the T4 transporter OATP1C1 and DIO2 in local T3 formation. Strikingly, THRB was mainly present in two classes of interneurons: a majority expressing CALB2/calretinin, from the caudal ganglionic eminence, and in somatostatin-expressing interneurons from the medial ganglionic eminence. By contrast, many cell types express SLC16A2 and THRA. CONCLUSIONS SLCO1C1 and DIO2 coexpression in the outer radial glia, the universal stem cell of the cerebral cortex, highlights the likely importance of brain-generated T3 in neurogenesis. The unique expression of THRB in discrete subsets of interneurons is a novel finding whose pathophysiological meaning deserves further investigation.