Miracle-dz/UniFAR-FTUs huggingface dataset:
Towards a More Standardized Approach to Pathologic Reporting of Pancreatoduodenectomy Specimens for Pancreatic Ductal Adenocarcinoma

Supplemental Digital Content is available in the text. In recent literature and international meetings held, it has become clear that there are significant differences regarding the definition of what constitutes as margins and how best to document the pathologic findings in pancreatic ductal adenocarcinoma. To capture the current practice, Pancreatobiliary Pathology Society (PBPS) Grossing Working Group conducted an international multispecialty survey encompassing 25 statements, regarding pathologic examination and reporting of pancreatic ductal adenocarcinoma, particularly in pancreatoduodenectomy specimens. The survey results highlighted several discordances; however, consensus/high concordance was reached for the following: (1) the pancreatic neck margin should be entirely submitted en face, and if tumor on the slide, then it is considered equivalent to R1; (2) uncinate margin should be submitted entirely and perpendicularly sectioned, and tumor distance from the uncinate margin should be reported; (3) all other surfaces (including vascular groove, posterior surface, and anterior surface) should be examined and documented; (4) carcinoma involving separately submitted celiac axis specimen should be staged as pT4. Although no consensus was achieved regarding what constitutes R1 versus R0, most participants agreed that ink on tumor or at and within 1 mm to the tumor is equivalent to R1 only in areas designated as a margin, not surface. In conclusion, this survey raises the awareness of the discordances and serves as a starting point towards further standardization of the pancreatoduodenectomy grossing and reporting protocols.
Combinations of self‐reported rhinitis, conjunctivitis, and asthma predicts IgE sensitization in more than 25,000 Danes

Abstract Background Allergic rhinitis (AR), allergic conjunctivitis (AC), and asthma composing multiple phenotypes and improved understanding of these phenotypes and their respective risk factors are needed. Objectives The objective of this study was to define the prevalence of AR, AC, and asthma and their association with allergen‐specific immunoglobulin E (sIgE) sensitization in a large cohort of blood donors and identify risk factors. Methods From the nationwide population‐based Danish Blood Donor Study, 52,976 participants completed an electronic questionnaire including AR, AC, asthma, allergic predisposition, and childhood residence. Of these, 25,257 were additionally tested for sIgE to inhalation allergens (Phadiatop). Results The prevalence of sIgE sensitization, AR, AC, and asthma was 30%, 19%, 15%, and 9%, respectively. The youngest birth cohorts had the highest prevalence of sIgE sensitization and symptoms of asthma, AR, and AC, and for asthma, they apparently experienced symptoms at an earlier age. The sIgE sensitization was positively associated with male sex. The sIgE seroprevalence was higher in participants with both AR and AC (ARC) than in participants with either AR or AC. Allergic predisposition and sIgE sensitization increased the risk of the diseases, while farm upbringing was associated with reduced prevalence of ARC, however, only in sIgE sensitized participants. Conclusion Birth year, childhood residence, sIgE sensitization, and allergic predisposition were associated with asthma, AR, and AC prevalence. Individuals with self‐reported ARC represent a primarily sIgE‐positive phenotype, while those with either AR or AC represent more diverse phenotypes.
Is the routine placement of a feeding jejunostomy during esophagectomy worthwhile?-a systematic review and meta-analysis.

BACKGROUND Malnutrition dramatically increases the risk of postoperative complications and delays patient recovery. Therefore, a feeding jejunostomy tube (FJT) is routinely placed during esophagectomy to maintain the postoperative nutrition supply. However, recently published studies have questioned the need of a FJT in every esophageal cancer patient. Because most patients can resume oral intake shortly after surgery, the nutrition-providing function of a FJT becomes much less critical. In contrast, FJT-related complications could be severe. METHODS Relevant publications were found out by systemic searching of four medical databases (Pubmed, EMBASE, Medline, and Cochrane Center Register of Controlled Trials). By reading the titles and the abstracts, potentially relevant studies were screened from the search results. The incidence of postoperative complications and FJT-related complications were calculated and compared to evaluate the efficacy of a FJT. RESULTS Eighteen studies were included in the meta-analysis. The no-FJT group had a similar or even lower incidence of postoperative complications [anastomotic leakage (AL), pulmonary complications, and wound infections] compared with the FJT group. Ileus and FJT site infections were the most common FJTrelated complications. The incidence of ileus was approximately 6% (95% CI: 3-12%), and over 63% of the patients with an ileus required re-operation to relieve the obstruction. The pooled mean rate of FJT site infections was 7% (95% CI: 6-9%). Approximately 7% of patients had dysfunction (obstruction or dislocation) of the jejunostomy tube (95% CI: 3-14%). CONCLUSIONS The non-selective placement of a FJT during esophagectomy provides few benefits to the patients and may even increase the risk of postoperative complications. Therefore, an intraoperative FJT should be selectively prescribed, but not routinely in the surgical treatment of esophageal cancer.
The effect of Tai Chi on the pulmonary rehabilitation of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

BACKGROUND The effectiveness of Tai Chi for chronic obstructive pulmonary disease (COPD) so far is unclear. The present systematic review aimed to determine the influence of Tai Chi among people with COPD. METHODS We searched six electronic databases for relevant studies in September, 2019. The methods of standard meta-analysis were used for identifying relevant studies, quality appraisal, and synthesis. The primary outcomes were six-minute walking distance (6MWD), percentage predicted forced expiratory flow volume in the first second (%PredFEV1), and St. George's Respiratory Questionnaire (SGRQ) score. RESULTS A total of 23 studies including 1663 participants were included in the meta-analysis. The pooled data showed that the Tai Chi group was associated with a significant improvement in 6MWD [mean difference (MD) 40.83 m, 95% CI: 32.47 to 49.19], %PredFEV1 (MD 1.67%, 95% CI: 0.41 to 2.93), SGRQ score (MD -6.57, 95% CI: -10.17 to -2.98), and Chronic Respiratory Disease Questionnaire (CRQ) (MD 1.60, 95% CI: 0.89 to 2.30) relative to the blank control population. When compared with breathing exercises, the 6MWD was significantly enhanced with Tai Chi (MD 14.15 m, 95% CI: 3.76 to 24.53). Finally, when compared with breathing and walking exercises, Tai Chi was associated with a significant improvement in 6MWD (MD 7.68 m, 95% CI: 2.28 to 13.09 m) and SGRQ score (MD -6.31, 95% CI: -9.13 to -1.48). CONCLUSIONS Tai Chi may have the potential to reduce dyspnoea, enhance exercise capacity, and improve the quality of life in COPD patients. People with COPD may obtain benefit from practicing Tai Chi.
Study on the Prognostic Values of Dynactin Genes in Low-Grade Glioma

Objective: This present study aims to investigate the potential prognostic values of dynactin genes (DCTN) for predicting the overall survival (OS) in low-grade glioma (LGG) patients. Methods: The DCTN mRNA expression data were downloaded from The Cancer Genome Atlas database containing 518 patients with LGG. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses for DCTN genes were performed by using Database for Annotation, Visualization, and Integrated Discovery platform, and their enrichment results were verified by using the Biological Networks Gene Ontology tool. Next, the correlations between DCTN genes and LGG were identified by Pearson correlation coefficient analysis. The OS was estimated by Kaplan-Meier survival analysis. The cBio Cancer Genomics Portal was used to analyze the mutations of DCTN genes and their effects on the prognosis of LGG. The correlation between the abundance of immune infiltration and tumor purity of DCTN genes were predicted by The Tumor Immune Estimation Resource. Results: Our research showed that the mRNA expression of DCTN4 in tumor tissues was much higher (P < 0.01) than that in normal tissues. Meanwhile, there was a certain correlation between the DCTN genes. Survival analysis showed that the high expression of DCTN1, DCTN3, DCTN4, DCTN6, and their co-expression were significantly correlated with favorable OS in LGG patients (P < 0.05). In DCTN2, a high mutation rate was observed. Further research showed that the genetic alteration in DCTN genes was related to a poor OS and progression-free survival of LGG patients. The expression of DCTN genes had a certain correlation with immune infiltrating cells. Conclusion: Our study showed that the high expressions of DCTN1, DCTN3, DCTN4, and DCTN6 were associated with a favorable OS of LGG patients, indicating that these DCTN genes are potential biomarkers for evaluating the prognosis of LGG patients.
Culture strategy as a modulator of target assessments: Functionality of suspension versus hanging drop‐derived choriocarcinoma spheroids as in vitro model of embryo implantation

The choriocarcinoma spheroid model has been amply applied to study the underlying molecular mechanism of implantation. Reproducibility and functionality of spheroid tumor models were addressed precisely. To mimic embryo‐endometrium crosstalk, no functional characteristics of spheroids have been provided based on culture strategies. In this study, choriocarcinoma spheroids were provided as suspension culture (SC) or hanging drop culture (HDC). Primary assessments were performed based on morphology, cellular density, and hormonal secretion. Spheroid‐endometrial cross talk was assessed as coculture procedures. Further, alkaline phosphatase (ALP) activity and expression of genes involved in attachment, invasion, and inducing migration were quantified. We found HDC spheroids provided a homogenous‐shaped aggregate with a high grade of viability, cellular integration, hormonal secretion, and the dominant role of WNTs expression in their microarchitecture. SC spheroids showed a higher level of ALP activity and the expression of integrated genes in modulating attachment, invasion, and migration abilities. Spheroid confrontation assays clearly clarified the superiority of SC spheroids to crosstalk with epithelial and stromal cells of endometrium in addition to motivating an ideal endometrial response. Conclusively, culture strategies by affecting various molecular signaling pathways should be chosen precisely according to specific target assessments. Specifically, SC assumed as an ideal model in spheroid‐endometrial cross talk.
The current paradigm for biologic initiation: a mixed-methods exploration of practices, unmet needs, and innovation opportunities in self-injection training

ABSTRACT Background Self-injection, particularly of biologics, has become a mainstay of chronic disease management. Despite labeling requirement for healthcare provider (HCP) training, current injection initiation experiences have been shown to be suboptimal. This study characterizes gaps in training and support during initiation and identifies rationales to inform solutions. Methods We enrolled HCPs (n = 18) performing routine biologic initiation and patients (n = 24) currently self-injecting biologics. Participants completed activities through an online, remote ethnography tool. We conducted two focus groups with biologic-naïve patients (n = 5). Data was analyzed using thematic frameworks, Q methodology, and quantitative assessments. Results Our results suggest considerable gaps exist. Analysis revealed five common themes that could explain these gaps: 1) minimal biologic-specific professional instruction is provided to HCPs; 2) nuanced injection use-steps are not universally understood; 3) no one stakeholder currently ‘owns’ training; 4) support offered by HCPs and manufacturers is perceived as biased; and 5) emotional burden is not accounted for. Conclusions Our study suggests optimizing several elements to facilitate successful initiations, including structured sessions, improved HCP injection device knowledge, demo-device practice, and focus on both emotional and mechanical aspects. Aligning these factors has potential to increase patient confidence, reduce burden on HCPs, and improve probability of success on therapy.
Update on drug-drug interaction at organic cation transporters: mechanisms, clinical impact, and proposal for advanced in vitro testing

ABSTRACT Introduction: Organic cation transporters collectively called OCTs belong to three gene families (SLC22A1 OCT1, SLC22A2 OCT2, SLC22A3 OCT3, SLC22A4 OCTN1, SLC22A5 OCTN2, SLC29A4 PMAT, SLC47A1 MATE1, and SLC47A1 MATE2-K). OCTs transport structurally diverse drugs with overlapping selectivity. Some OCTs were shown to be critically involved in pharmacokinetics and therapeutic efficacy of cationic drugs. Drug-drug interactions at individual OCTs were shown to result in clinical effects. Procedures for in vitro testing of drugs for interaction with OCT1, OCT2, MATE1, and MATE2-K have been recommended. Areas covered: An overview of functional properties, cation selectivity, location, and clinical impact of OCTs is provided. In addition, clinically relevant drug-drug interactions in OCTs are compiled. Because it was observed that the half maximal concentration of drugs to inhibit transport by OCTs (IC 50) is dependent on the transported cation and its concentration, an advanced protocol for in vitro testing of drugs for interaction with OCTs is proposed. In addition, it is suggested to include OCT3 and PMAT for in vitro testing. Expert opinion: Research on clinical roles of OCTs should be reinforced including more transporters and drugs. An improvement of the in vitro testing protocol considering recent data is imperative for the benefit of patients.
Stretch-Shortening Cycle Potentiation and Resistance Training-Induced Changes in Walking Economy/Ease and Activity-Related Energy Expenditure in Older Women

Abstract Hunter, GR, Singh, H, Martins, C, Baranauskas, MN, and Carter, SJ. Stretch-shortening cycle potentiation and resistance training-induced changes in walking economy/ease and activity-related energy expenditure in older women. J Strength Cond Res 35(5): 1345–1349, 2021—Use of elastic energy to improve economy and ease of walking may be important for older adults. The purpose of this investigation was to determine whether baseline (i.e., untrained) stretch-shortening cycle potentiation (SSCP) was associated with potential changes in free-living activity-related energy expenditure (AEE) after supervised exercise training. Sedentary, postmenopausal women (n = 64) between 60 and 74 years of age were evaluated before and after 16 weeks of combined aerobic and resistance training. Assessments included: (a) body composition (dual-energy X-ray absorptiometry), (b) resting energy expenditure (indirect calorimetry), (c) submaximal and maximal walking (treadmill/indirect calorimetry), (d) total energy expenditure (doubly labeled water), and (e) one repetition maximum performed on an incline leg press and SSCP (calculated as the difference between concentric and countermovement leg press throw). Results indicated that baseline SSCP was related (r = −0.29; p < 0.02) to changes in AEE. However, subjects who possessed a high baseline SSCP did not increase SSCP or AEE, whereas subjects with low to moderate baseline SSCP demonstrated a significant increase in both SSCP (low +0.54 and moderate +0.47 m·s−1) and AEE (low +158 and moderate +333 kcal·d−1) post-training (all p less than 0.05). Our findings suggest that among subjects with low to moderate baseline SSCP, 16 weeks of combined aerobic and resistance training can increase SSCP and free-living AEE. However, subjects with high baseline SSCP may require tailored exercise to increase SSCP and possibly AEE.
Chronic rhinosinusitis with and without nasal polyps and asthma: Omalizumab improves residual anxiety but not depression

Abstract Background Chronic rhinosinusitis (CRS) has a high prevalence of anxiety and depression. It is currently uncertain if treatment in patients with CRS with or without nasal polyps (CRSwNP and CRSsNP) has any impact on improving mental health outcomes. The aims here were to document anxiety and depression in patients with severe CRS and asthma already treated with appropriate medical therapy. We then evaluated whether further maximal treatment with omalizumab improved anxiety and/or depression alongside improvements in CRS and coassociated asthma. Methods Hospital Anxiety and Depression Scale (HADS) scores along with measures of CRS and asthma severity were recorded according to CRSwNP and CRSsNP status in n = 95 patients with severe CRS and asthma. Of this group, a further n = 23 had omalizumab for associated allergic asthma. Follow‐up measures were collected 16 weeks after omalizumab treatment. Results HADS anxiety and depression prevalence in CRS were 49.47 % and 38.95%, respectively. Within the CRSwNP and CRSsNP group 53.06% and 45.66% had raised HADS‐anxiety scores. Abnormal HADS‐depression scores were present in 40.82% and 36.95% of the CRSwNP and CRSsNP groups, respectively. Correlations for sinonasal outcome test‐22 (SNOT‐22) versus HADS total was r = 0.59 p < 0.0001, HADS‐anxiety r = 0.56 p < 0.0001 and HADS‐depression r = 0.49 p < 0.0001. Omalizumab improved anxiety in CRS (p < 0.0001) regardless of nasal polyp status (CRSwNP p = 0.0042 and CRSsNP p = 0.0078). Depression scores did not improve in either group. SNOT‐22 (p = 0.0006), asthma control questionnaire‐7 (p = 0.0019) and mini‐asthma quality of life questionnaire including emotional function (p = 0.0003 and p = 0.0009, respectively) all improved in both subgroups. Conclusion In CRS and asthma, anxiety scores but not depression improved after omalizumab treatment. Anxiety may be closely related to airway disease severity, but depression may be independent of airway disease itself. If so, a separate mental health care pathway is needed for CRS patients with depression.
Skin Barrier and Inflammation Genes Associated with Atopic Dermatitis are Regulated by Interleukin-13 and Modulated by Tralokinumab In vitro

Society for Publication of Acta Dermato-Venereologica 1https://doi.org/10.2340/00015555-3810 Atopic dermatitis (AD) is a chronic, pruritic skin disease characterized by type 2 immune-mediated inflammation and skin barrier dysfunction (1). The impaired skin barrier in AD is related to decreased expression of epidermal barrier proteins and to changes in lipid composition in the stratum corneum. AD lesions are characterized by increased expression of pro-inflammatory mediators, such as chemokines, leading to recruitment of immune cells, which may further exacerbate the inflammation. Interleukin (IL)-13 and IL-4 are the signature type 2 cytokines involved in AD. These cytokines both signal through the type II receptor, composed of IL-4Rα and IL-13Rα1, and display functional redundancy in cells harbouring this receptor, including keratinocytes and fibroblasts. This is in contrast to cells, such as T lymphocytes, containing the type I receptor (IL-4Rα combined with the common gamma chain), which is only used by IL-4 for signalling. Monoclonal antibodies targeting IL-4Rα (dupilumab) or IL-13 (tralokinumab and lebrikizumab) have demonstrated clinical efficacy in AD (2–4). Interestingly, protein levels of IL-13, but not IL-4, are consistently detected and shown to be increased in AD skin across studies (5, 6). Furthermore, 3 recently published studies using RNA-sequencing of AD biopsies found increased levels of IL13 in lesional and non-lesional AD skin, whereas expression of IL4 was undetectable or very low (7–9). Independent studies also found a correlation between expression levels of IL-13 at mRNA or protein level in lesional AD skin and disease severity (6, 7). The aim of the current study is to further investigate effects of IL-13 on AD-associated genes in human skin cells and to provide molecular insights into the mechanism of action of tralokinumab, a fully human IgG4 monoclonal antibody that specifically neutralizes IL-13.
Physical Training Inhibits the Fibrosis Formation in Alzheimer's Disease Kidney Influencing the TGFβ Signaling Pathways.

BACKGROUND Alzheimer's disease (AD) is a neurodegenerative illness, with several peripheral pathological signs such as accumulation of amyloid-β (Aβ) plaques in the kidney. Alterations of transforming growth factor β (TGFβ) signaling in the kidney can induce fibrosis, thus disturbing the elimination of Aβ. OBJECTIVE A protective role of increased physical activity has been proven in AD and in kidney fibrosis, but it is not clear whether TGFβ signalization is involved in this effect. METHODS The effects of long-term training on fibrosis were investigated in the kidneys of mice representing a model of AD (B6C3-Tg(APPswe,PSEN1dE9)85Dbo/J) by comparing wild type and AD organs. Alterations of canonical and non-canonical TGFβ signaling pathways were followed with PCR, western blot, and immunohistochemistry. RESULTS Accumulation of collagen type I and interstitial fibrosis were reduced in kidneys of AD mice after long-term training. AD induced the activation of canonical and non-canonical TGFβ pathways in non-trained mice, while expression levels of signal molecules of both TGFβ pathways became normalized in trained AD mice. Decreased amounts of phosphoproteins with molecular weight corresponding to that of tau and the cleaved C-terminal of AβPP were detected upon exercising, along with a significant increase of PP2A catalytic subunit expression. CONCLUSION Our data suggest that physical training has beneficial effects on fibrosis formation in kidneys of AD mice and TGFβ signaling plays a role in this phenomenon.
Rate of thrombosis in children and adolescents hospitalized with COVID-19 or MIS-C

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is associated with thrombotic complications in adults, but the incidence of COVID-19 related thrombosis in children and adolescents is unclear. Most children with acute COVID-19 have mild disease, but coagulopathy has been associated with multisystem inflammatory syndrome in children (MIS-C), a post-infectious complication. We conducted a multicenter retrospective cohort study to determine the incidence of thrombosis in children hospitalized with COVID-19 or MIS-C and to evaluate associated risk factors. We classified patients into one of three groups for analysis: COVID-19, MIS-C, or asymptomatic SARS-CoV-2. Among a total of 853 admissions (426 COVID-19, 138 MIS-C, and 289 asymptomatic SARS-CoV-2) in 814 patients, there were 20 patients with thrombotic events (TE) (including 1 stroke). Patients with MIS-C had the highest incidence (6.5%, 9/138) versus COVID-19 (2.1%, 9/426) or asymptomatic SARS-CoV-2 (0.7%, 2/289). In patients with COVID-19 or MIS-C, the majority of thrombotic events (89%) occurred in patients ≥12 years. Patients 12 years with MIS-C had the highest rate of thrombosis at 19% (9/48). Notably, 71% of TE that were not present on admission occurred despite thromboprophylaxis. Multivariable analysis identified the following as significantly associated with thrombosis: age ≥12 years, cancer, presence of a central venous catheter, and MIS-C. In patients with COVID-19 or MIS-C, hospital mortality was 2.3% (13/564), but was 28% (5/18) in patients with thrombotic events. Our findings may help inform pediatric thromboprophylaxis strategies.