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The simulation of internal climate variability is key to understanding climate change. Internal fluctuations can fully obscure or amplify the underlying climate-change signal in many fields over years to decades. The Pacific Decadal Oscillation (PDO) is an important mechanism that dominates interdecadal climate variations. Here, the capacity of 36 Coupled Model Intercomparison Project Phase 6 (CMIP6) models for reproducing the PDO during the period 1901-2014 was evaluated across spatial pattern, amplitude, periodicity and phase aspects. The results suggested that approximately 71% of the models were capable of capturing the spatial pattern of the PDO. However, most of the other models underestimated the percentage of the variance explained and the pattern amplitude. CMIP6 models can capture the periodicity over shorter periods (

BACKGROUND: The World Health Organization Classification (WHO) of Urinary and Male Genital Tumors has recently been updated to its 5th edition. The new edition presents a comprehensive approach to the classification of urinary and male genital tumors with an incorporation of morphologic, clinical, and genomic data. OBJECTIVE: This review aims to update the new classification of bladder cancer in the 5th edition and to highlight important changes in nomenclatures, diagnostic criteria, and molecular characterization, as compared to the 4th edition. METHODS: The pathologic classification of bladder cancer in the 5th edition of WHO Classification of Urinary and Male Genital Tumours was compared to that in the 4th edition. PubMed was searched using key words, including bladder cancer, WHO 1973, WHO 1998, WHO 2004, WHO 2016, histology, pathology, genomics, and molecular classification in the time frame from 1973 to August of 2022. Other relevant papers were also consulted, resulting in the selection of 81 papers as references. RESULTS: The binary grading of papillary urothelial carcinoma (UC) is practical, but it may be oversimplified and contribute to “grade migration” in recent years. An arbitrary cutoff (5%) has been proposed for bladder cancers with mixed grades. The diagnosis of papillary urothelial neoplasm with low malignant potential has been dramatically reduced in recent years because of overlapping morphology and treatment with low-grade papillary UC. An inverted growth pattern should be distinguished from true (or destructive) stromal invasion in papillary UC. Several methods have been proposed for pT1 tumor substaging, but it is often challenging to substage pT1 tumors in small biopsy specimens. Bladder UC shows a high tendency for divergent differentiation, leading to several distinct histologic subtypes associated with an aggressive clinical behavior. Molecular classification based on the genomic analysis may be a useful tool in the stratification of patients for optimal treatment. CONCLUSIONS: The 5th edition of WHO Classification of Urinary and Male Genital Tumours has made several significant changes in the classification of bladder cancer. It is important to be aware of these changes and to incorporate them into routine clinical practice.

Purpose The purpose of this study is to assess the validity and predictability of insights from the investment model (IM) in the context of strategic manufacturer–industrial supplier relationships. IM is a theoretical model in social psychology pertaining to interpersonal relationship discontinuity. This formal empirical test of IM in a different context supports vertical theory borrowing and minimizes the risk of committing atomistic fallacy. Design/methodology/approach Data collected from 256 sourcing professionals participating in a scenario-based role-playing experiment were analyzed via structural equation modeling. The authors also performed bootstrapping to assess indirect effects. Findings The IM is generally applicable to the context of interfirm relationship dissolution. Relative to the original context of interpersonal relationship dissolution, three nuances are detected: investment size as an antecedent has lowered prominence in influencing commitment; satisfaction level, quality of alternatives and investment size have non-orthogonal effects on commitment; and satisfaction level influences relationship continuity through and beyond commitment. Research limitations/implications The empirical findings broaden boundary conditions for IM insights. Beyond interpersonal relationship dissolution, the IM appears to also describe, explain and predict interfirm relationship dissolution. Practical implications Keeping the manufacturer satisfied is critical. Moreover, suppliers should be cautious when entering joint product development agreements. Originality/value This study appears to be among the first to formally validate the applicability of IM insights as they pertain to the dissolution of strategic manufacturer–industrial supplier relationships.

Accurate reduction is of vital importance in the treatment of zygomaticomaxillary complex (ZMC) fractures. Computer-assisted navigation systems (CANS) have been employed in ZMC fractures to improve the accuracy of surgical reduction. However, randomized controlled trials on this subject are rare and the benefits of CANS remain controversial. The aim of this study was to compare reduction errors between navigation-aided and conventional surgical treatment for ZMC fractures. Thirty-eight patients with unilateral type B ZMC fractures were enrolled. Preoperative computed tomography data were imported into ProPlan software for virtual surgical planning. Open reduction and internal fixation was performed with CANS (experimental group) or without CANS (control group). Postoperative computed tomography scans were obtained to examine the difference between surgical planning and the actual postoperative outcome, namely reduction errors. The median translational reduction errors in the X, Y, and Z axes were 0.80 mm, 0.40 mm, and 0.80 mm, respectively, in the experimental group and 0.53 mm, 0.86 mm, and 0.83 mm, respectively, in the control group (P0.05). The median rotational reduction errors in pitch, roll, and yaw were 0.92°, 2.47°, and 1.54°, respectively, in the experimental group and 1.45°, 3.68°, and 0.76°, respectively, in the control group (P0.05). In conclusion, compared with conventional reduction surgery, navigation-aided surgery showed no significant improvement in reduction accuracy in the treatment of type B ZMC fractures (Chinese Clinical Trial Registry, registration number ChiCTR1800015559).

Insurance companies are increasingly making unilateral determinations of admission status for primary total knee arthroplasty (TKA). These determinations may differ from those based on surgeon-derived criteria for outpatient knee replacement. The goal of this study is to determine if insurance company determinations of outpatient status are as reliable as surgeon-derived criteria in predicting outpatient discharge after TKA.We retrospectively reviewed 709 patients who were preoperatively authorized for outpatient TKA. Patients were stratified into 2 groups: "outpatient per surgeon" (appropriate for outpatient surgery per institutional protocols) or "outpatient per insurance" (appropriate for inpatient surgery per institutional protocols but denied inpatient status by insurance). The primary endpoint of this study was the conversion rate of outpatient to inpatient stay. Univariate logistic regression was performed to compare the odds of conversion to inpatient stay between outpatient per surgeon and outpatient per insurance procedures and other covariates.The cohort included 434 outpatient per insurance (61.2%) and 275 outpatient per surgeon (38.8%) patients. Surgeons accurately predicted outpatients' discharge 92.0% of the time, while insurance companies did so 81.3% of time (P.001). Outpatient per insurance procedures (odds ratio [OR] 2.20, P = .003) and body mass index35 kg/mDetermining inpatient versus outpatient status is a complex decision involving both clinical and social factors. Surgeons accurately predicted outpatient discharge 92% of the time. Moreover, outpatient per insurance procedures were twice as likely to be converted to inpatient status. Therefore, insurance companies should leave deciding admission status up to both the patient and surgeon.

Objectives Quantifying the number of older adults that are food insecure in a specific geographic area is critical in developing and scaling public health prevention and response programs at the local level. However, current estimates of older adult food insecurity only consider financial constraints, following the same methodology as the general population, even though the drivers for older adults are different and multidimensional. This study aims to build a general approach to quantify the food-insecurity among older adults at the local level, using publicly available data that can be easily obtained across the country. Methods 13 risk factors for food insecurity among older adults were identified leveraging existing studies, following the Social Ecological Model (SEM), and the weighted impact of each factor was determined. Publicly available data sources were identified for each factor, ZIP code level data was compared to national averages, and the weighted data for each factor were aggregated to determine the overall food insecurity at the local level. Results Based on the averaged odds ratios across all the studies, of the 13 risk factors, beyond financial constraints, having a disability was the most impactful factor and distance to the nearest grocery store was the least impactful. A ZIP code level model of Honolulu County was developed as an example to demonstrate the approach, showing that food insecurity among older adults in the county was 2.5 times that which was reported from the Current Population Survey (16.5% versus 6.5%). Conclusion This evidence-based model considered factors that impact food insecurity among older adults across all the spheres of the SEM. The drivers of food insecurity among older adults are different than the drivers for the general population, resulting in a higher percentage of older adults being food insecure than currently reported.

Quality of transmission (QoT) prediction, one of the essential technologies to enable low-margin automatic optical networks, has recently attracted increasing interest among researchers [1]. Analytical model-based QoT estimation, such as the GNPy software, provides system-level optimization for static operations [2]. However, in low-margin dynamic optical networks, QoTs should be predicted based on traffic payload, link configurations, and other parameters to obtain precise QoTs for dynamic configurations with further reduced link margins. In [3], a point-to-point multi-channel QoT prediction based on artificial neural networks(ANN) was proposed, however, lacking end-to-end solutions in terms of training and deployment. P. Safari, etc., developed a network-wide modelfor QoT classification based on a deep convolutional neural network (DCNN) model [4]. However, the complex DCNN model strongly depends on network typologies and requires a huge amount of data from the whole network. which makes it infeasible to train and deploy the model in a practical optical network. In this paper, two cascaded multi-channel ANN models are developed, co-trained, and demonstrated to predict link penalties over a 986-km field-trial testbed consisting of two links and ROADMs. With the two-cascaded ANN setting, the QoT of a channel over the two links is predicted considering traffic payloads in two links with precision of ± 0.16 dB. The co-training of the two cascaded penalty prediction models also provides a feasible solution to provide network-level QoT predictions.

The Cdc48 AAA+ ATPase is an abundant and essential enzyme that unfolds substrates in multiple protein quality control pathways. The enzyme includes two conserved AAA+ ATPase cassettes, D1 and D2, that assemble as hexameric rings with D1 stacked above D2. Here, we report an ensemble of structures of Cdc48 affinity purified from lysate in complex with the adaptor Shp1 in the act of unfolding substrate. Our analysis reveals a continuum of structural snapshots that spans the entire translocation cycle. These data reveal new elements of Shp1-Cdc48 binding and support a “hand-over-hand” mechanism in which the sequential movement of individual subunits is closely coordinated. D1 hydrolyzes ATP and disengages from substrate prior to D2, while D2 rebinds ATP and re-engages with substrate prior to D1, thereby explaining the dominant role played by D2 in substrate translocation/unfolding.

SUMMARYThe cytosolic Chaperonin Containing Tailless polypeptide 1 (CCT) complex is an essential protein folding machine with a diverse clientele of substrates, including many proteins with β- propeller domains. Here, we determined structures of CCT in complex with its accessory co chaperone, phosducin-like protein 1 (PhLP1), in the process of folding Gβ5, a component of Regulator of G protein Signaling (RGS) complexes. Cryo-EM and image processing revealed an ensemble of distinct snapshots that represent the folding trajectory of Gβ5from an unfolded molten globule to a fully folded β-propeller. These structures reveal the mechanism by which CCT directs Gβ5folding through initiating specific intermolecular contacts that facilitate the sequential folding of individual β-sheets until the propeller closes into its native structure. This work directly visualizes chaperone-mediated protein folding and establishes that CCT directs folding by stabilizing intermediates through interactions with surface residues that permit the hydrophobic core to coalesce into its folded state.

Metastasis is the deadliest phase of cancer progression. Experimental models using immunodeficient mice have been used to gain insights into the mechanisms of metastasis. We report here the identification of a “metastasis aggressiveness gene expression signature” derived using human melanoma cells selected based on their metastatic potentials in a xenotransplant metastasis model. Comparison with expression data from human melanoma patients shows that this metastasis gene signature correlates with the aggressiveness of melanoma metastases in human patients. Many genes encoding secreted and membrane proteins are included in the signature, suggesting the importance of tumor-microenvironment interactions during metastasis. (Mol Cancer Res 2008;6(5):760–9)

Supplementary Table S4 from Gene Expression Changes in an Animal Melanoma Model Correlate with Aggressiveness of Human Melanoma Metastases

Supplementary Figures S1-S2 from Gene Expression Changes in an Animal Melanoma Model Correlate with Aggressiveness of Human Melanoma Metastases

Although many studies have observed genome-wide host transposon expression alteration during viral infection, the mechanisms of induction and the impact on the host remain unclear. Utilizing recently published influenza A virus (IAV) time series data and ENCODE functional genomics data, we characterized virus induced host differentially expressed transposons (virus-induced-TE) by investigating genome-wide spatial and functional relevance between the virus-induced-TEs and epigenomic markers (e.g. histone modification and chromatin remodelers). We found that a significant fraction of virus-induced-TEs are derived from host enhancer regions, where CHD4 binding and/or H3K27ac occupancy is high or H3K9me3 occupancy is low. By overlapping virus-induced-TEs to human enhancer RNAs (eRNAs), we discovered that a proportion of virus-induced-TEs are either eRNAs or part of enhancer RNAs. Upon further analysis of the eRNA targeted genes, we found that the virus-induced-TE related eRNA targets are overrepresented in differentially expressed host genes of IAV infected samples. Our results suggest that changing chromatin accessibility from repressive to permissive in the transposon docked enhancer regions to regulate host downstream gene expression is potentially one of the virus and host cell interaction mechanisms, where transposons are likely important regulatory genomic elements. Our study provides a new insight into the mechanisms of virus-host interaction and may lead to novel strategies for prevention and therapeutics of IAV and other virus infectious diseases.

We present a high sensitivity, ground-based spectral line survey of low-J carbon monoxide (CO(Jup → Jup − 1) with Jup = 1, 2, 3) and neutral carbon [CI] 3P1−3P0 ([CI](1–0)) in 36 local ultra-luminous infrared galaxies (ULIRGs) and 4 additional LIRGs, all of which have previous Herschel OH 119 μm observations. The study is based on new single-dish observations conducted with the Atacama Pathfinder Experiment (APEX) and complemented with archival APEX and Atacama Large Millimeter Array (ALMA and ACA) data. Our methods are optimized for a multi-tracer study of the total molecular line emission from these ULIRGs, including any extended low-surface-brightness components. We find a tight correlation between the CO and [CI] line luminosities, which suggests that the emission from CO(1–0) (and CO(2–1)) arises from similar regions as the [CI](1–0), at least when averaged over galactic scales. By using [CI] to compute molecular gas masses, we estimate a median CO-to-H2 conversion factor of ⟨αCO⟩ = 1.7 ± 0.5 M⊙ (K km s−1pc2)−1 for ULIRGs. We derive median galaxy-integrated CO line ratios of 〈r21〉 = LCO(2-1)′/LCO(1-0)′ = 1.09, 〈r31〉 = LCO(3-2)′/LCO(1-0)′ = 0.76, and 〈r32〉 = LCO(3-2)′/LCO(2-1)′ = 0.76, significantly higher than normal star-forming galaxies, confirming the exceptional molecular gas properties of ULIRGs. We find that the r21 and r32 ratios are poor tracers of CO excitation in ULIRGs, while r31 shows a positive trend with LIR and star formation rates and a negative trend with the H2 gas depletion timescales (τdep). Our investigation of CO line ratios as a function of gas kinematics shows no clear trends, except for a positive relation between r21 and σv, which can be explained by CO opacity effects. These ULIRGs are also characterized by high L[CI](1-0)′/LCO(1-0)′ ratios, with a measured median value of ⟨rCICO⟩ = 0.18, higher than values from previous interferometric studies that were affected by missing [CI] line flux. The rCICO values do not show a significant correlation with any of the galaxy properties investigated, including OH outflow velocities and equivalent widths. We find that the widths of [CI](1–0) lines are ∼10% smaller than those of CO lines, and that this discrepancy becomes more significant in ULIRGs with broad lines (σv > 150 km s−1) and when considering the high-v wings of the lines. This suggests that the low optical depth of [CI] can challenge its detection in diffuse, low-surface-brightness outflows and, therefore, its use as a tracer of CO-dark H2 gas in these components. Finally, we find that higher LAGN are associated with longer τdep, consistent with the hypothesis that active galactic nucleus feedback may reduce the efficiency of star formation. Our study highlights the need for sensitive single-dish multi-tracer H2 surveys of ULIRGs that are able to recover the flux that is missed by interferometers, especially in the high-frequency lines such as [CI]. The Atacama Large Aperture Submillimeter Telescope (AtLAST) will be transformational for this field.

SummaryAccumulating evidence indicate a strong link between neural signals and the immune system. Given neural signals constitute a large family that may be leveraged for communication, we systematically explored the neuro-immune regulation network in the periphery and uncovered a broad yet lineage selective expression of neuro-receptors on immune cells. We constructed a rich social immune network map showing the neural molecular pathways supporting the regulation of the immune system at steady state. Our results emphasize neuro-receptors role in the commitment and differentiation of B and T cells along their developmental process. We identified the immune cells’ functionality in the specific tissue is extensively shaped by the communication with the microenvironment and nervous systems via a rich alphabet of neural mediators. Collectively, our findings suggest neural genes are an integral part of the immune regulatory system and provide clear testable new avenues of experimental follow up for neuroimmunologists and immunologists alike.Abstract FigureHighlights160 neural genes potentially active in immune cells in the periphery with high specificity to lineageNeuro-receptors co-expressed in immune lineages are enriched for biological functionsChanges in neuro-receptors expression influence the HCS differentiation and commitmentImmune-microenvironment neural signaling architecture reflects tissue biological role

Background Hip resurfacing arthroplasty (HRA) and total hip arthroplasty (THA) are two treatment options for end-stage degenerative hip conditions. The objective of this single-center retrospective cohort study was to compare implant survival and patient-reported outcomes (PROs) in young patients (≤35 years) who underwent HRA or THA. Methods All patients aged 35 years or younger who underwent HRA or THA with a single high-volume arthroplasty surgeon between 2004 and 2015 were reviewed. The sample included 33 THAs (26 patients) and 76 HRAs (65 patients). Five-year implant survival and minimum 2-year PROs were compared between patient cohorts. Results Three patients in the THA group (9%) were revised within 5 years for instability (n = 1), squeaking (n = 1), or squeaking with a ceramic liner fracture (n = 1). No patients who underwent HRA were revised. The University of California, Los Angeles, activity score, modified Harris Hip score, and Hip Dysfunction and Osteoarthritis Outcome Scores for Joint Replacement increased by 74%, 64%, and 49%, respectively, among all patients. Compared to the HRA cohort, patients who underwent THA had lower preoperative and postoperative University of California, Los Angeles, activity, modified Harris Hip score, and Hip Dysfunction and Osteoarthritis Outcome Scores for Joint Replacement scores, yet there were no differences in the absolute improvements in any of the three measures between the two groups. Conclusions Excellent functional outcomes were seen in young patients undergoing either HRA or THA. Although young patients undergoing THA started at lower preoperative baseline and postoperative PROs than patients undergoing HRA, both groups improved by an equal amount after surgery, suggesting that both HRA and THA afford a similar degree of potential improvement in a young population.

BACKGROUND Early aseptic revision within 90 days after primary TKA is a devastating complication. The causes, complications, and rerevision risks of aseptic revision TKA performed during this period are poorly described. QUESTIONS/PURPOSES (1) What is the likelihood of re-revision within 2 years after early aseptic TKA revision within 90 days compared with that of a control group of patients undergoing primary TKA? (2) What are the indications for early aseptic TKA revision within 90 days? (3) What are the differences in revision risk between different indications for early aseptic revision TKA? METHODS Patients who underwent unilateral aseptic revision TKA within 90 days of the index procedure were identified in a national insurance claims database (PearlDiver Technologies) using administrative codes. The exclusion criteria comprised revision for infection, history of bilateral TKA, and age younger than 18 years. The PearlDiver database was selected for its large and geographically diverse patient base and the availability of outpatient follow-up data that are unavailable in other databases focused on inpatient care. A total of 481 patients met criteria for early aseptic revision TKA, with 14% (67) loss to follow-up at 2 years. This final cohort of 414 patients was compared with a control group of patients who underwent primary TKA without revision within 90 days. For the control group, 137,661 patients underwent primary TKA without early revision, with 13% (18,138) loss to follow-up at 2 years. Among these patients, 414 controls were matched using a one-to-one propensity score method; no differences in age, gender, and Charlson comorbidity index score were observed between the groups. Indications for initial revision and 2-year re-revision were recorded. The Kaplan-Meier method was used to assess survival between the early revision and control groups. RESULTS Two-year survivorship free from additional revision surgery was lower in the early aseptic revision cohort compared with the control (78% [95% confidence interval 77% to 79%] versus 98% [95% CI 96% to 99%]; p < 0.001). Among early revisions, 10% (43 of 414) of the patients underwent re-revision for periprosthetic infection with an antibiotic spacer within 2 years. The reasons for early aseptic revision TKA were instability/dislocation (37% [153 of 414]), periprosthetic fracture (23% [96 of 414]), aseptic loosening (23% [95 of 414]), pain (11% [45 of 414]), and arthrofibrosis (6% [25 of 414]). Early revision for pain was associated with higher odds of re-revision than early revisions performed for other all other reasons (44% [20 of 45] versus 29% [100 of 344]; odds ratio 2.0 [95% CI 1.0 to 3.7]; p = 0.04). CONCLUSION Acute early aseptic revision TKA carries a high risk of re-revision at 2 years and a high risk of subsequent periprosthetic joint infection. Patients who undergo an early revision should be carefully counseled regarding the very high risk of repeat revision and discouraged from having early revision unless the indications are absolutely clear and compelling. Early aseptic revision for pain alone carries an unacceptably high risk of repeat revision and should not be performed. Adjunctive measures for infection prophylaxis should be strongly considered. Specific interventions to reduce surgical complications in this subset of patients have not been adequately studied; additional investigation of strategies to minimize the risk of reoperation or infection is warranted. LEVEL OF EVIDENCE Level III, therapeutic study.

As COVID-19 pandemic approaching its third year, more data have shown that obesity and hypertriglyceridemia are the high-risk factors for the major complications such as acute respiratory distress syndrome, thromboembolism, coagulopathy and cytokine storm, which are responsible for the majority of disease severity and mortality. In this review article, we have analyzed the public available clinical reports and laboratory research results of the COVID-19 studies by researchers and clinicians of many nations around the world. Many of these reports covered COVID-19 patients of different ethnic groups. We suggested that obesity and high triglycerides are high risks for severe COVID-19 and death. We also summarized the possible underlying molecular mechanism likely connecting the severe COVID-19 with obesity and hypertriglyceridemia. From public health perspective, we highlight the importance of the healthy diet and lifestyle in fighting against SARS-CoV-2 virus in long period of time.

Adhesive capsulitis of the shoulder involves loss of passive range of motion with associated pain and can develop spontaneously, with no obvious injury or inciting event. The pathomechanism of this disorder remains to be elucidated, but known risk factors for adhesive capsulitis include diabetes, female sex, and thyroid dysfunction. Additionally, transcriptional profiling and pedigree analyses have suggested a role for genetics. Identification of elements of genetic risk for adhesive capsulitis using population-based techniques can provide the basis for guiding both the personalized treatment of patients based on their genetic profiles and the development of new treatments by identification of the pathomechanism.A genome-wide association study (GWAS) was conducted using the U.K. Biobank (a collection of approximately 500,000 patients with genetic data and associated ICD-10 [International Classification of Diseases, 10th Revision] codes), comparing 2,142 patients with the ICD-10 code for adhesive capsulitis (M750) to those without. Separate GWASs were conducted controlling for 2 of the known risk factors of adhesive capsulitis-hypothyroidism and diabetes. Logistic regression analysis was conducted controlling for factors including sex, thyroid dysfunction, diabetes, shoulder dislocation, smoking, and genetics.Three loci of significance were identified: rs34315830 (in WNT7B; odds ratio [OR] = 1.28; 95% confidence interval [CI], 1.22 to 1.39), rs2965196 (in MAU2; OR = 1.67; 95% CI, 1.39 to 2.00), and rs1912256 (in POU1F1; OR = 1.22; 95% CI, 1.14 to 1.31). These loci retained significance when controlling for thyroid dysfunction and diabetes. The OR for total genetic risk was 5.81 (95% CI, 4.08 to 8.31), compared with 1.70 (95% CI, 1.18 to 2.36) for hypothyroidism and 4.23 (95% CI, 2.32 to 7.05) for diabetes.The total genetic risk associated with adhesive capsulitis was significant and similar to the risks associated with hypothyroidism and diabetes. Identification of WNT7B, POU1F1, and MAU2 implicates the Wnt pathway and cell proliferation response in the pathomechanism of adhesive capsulitis.Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Introduction Recent clinical trials of heart failure with preserved ejection fraction (HFpEF) have observed varying patient profiles by ejection fraction (EF), with attenuation of treatment benefits as EF increases. In routine clinical practice, the degree to which patients hospitalized for HF with EF≥60% may differ from those with lower EF is unknown. Purpose To compare patient characteristics, treatment patterns, and clinical outcomes across the range of EF among patients hospitalized for HFpEF. Methods Using the Humedica electronic medical records database between Jan 2010 and Dec 2020, patients hospitalized for a primary diagnosis of HF with EF>40% and who were haemodynamically stable at admission, without concurrent acute coronary syndrome or end-stage renal disease, and treated with intravenous (IV) diuretic agents within 48 h of admission were identified. Patient characteristics, treatment patterns, and clinical outcomes were compared by EF ranges of 41–49%, 50–59%, and ≥60%. Results Of 47,026 patients hospitalized with HFpEF, 6,335 (13%) had EF 41–49%, 18,603 (40%) had EF 50–59%, and 22,088 (47%) had EF≥60%. Across all 3 groups, patients were similar with respect to age (median 77 years for each group), race (83–84% White, 12–13% Black), systolic blood pressure (137–138 mmHg at admission), and eGFR (63–64 mL/min/1.73 m2 at admission). With progressively higher EF group, the proportion of women increased (45% vs 54% vs 65%) and median NT-proBNP decreased (4,221 vs 2,945 vs 2,234 pg/mL). Patients with EF ≥60% had the lowest rates of coronary artery disease and atrial fibrillation, and the highest rates of chronic pulmonary disease (Figure 1, Panel A). Discharge medications were generally similar, with exception of less beta-blocker use and more calcium channel blocker use among those with EF ≥60% (Figure 1, Panel B). Discharge use of angiotensin receptor-neprilysin inhibitor and sodium glucose cotransporter-2 inhibitor therapies were each Conclusion In a contemporary real-world population of US patients hospitalized for HF with EF >40%, nearly half had an EF≥60%. While clinical profiles and discharge medications varied, post-discharge outcomes were similarly poor irrespective of EF. There remain important opportunities to improve the care and outcomes for patients with HF across the range of preserved ejection fraction. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): MyoKardia, Inc., a wholly owned subsidiary of Bristol Myers Squibb

Sweat glands are widely distributed in human skin, among which eccrine sweat glands play major roles in heat dissipation and sweat secretion. Sweat secretion is mainly regulated by nervous system and includes two processes of secretion of secretory coil and reabsorption of sweat duct, involving various ion channels and proteins such as calcium ion channel, potassium ion channel, sodium-potassium-chloride co-transporter 1, Best2 protein, aquaporin 5, cystic fibrosis transmembrane conductance regulator, and epithelial sodium ion channel. This paper reviews the nerve conduction system and various ion channels involved in sweat secretion of exocrine sweat glands in order to provide a theoretical basis for the study of regeneration, repair, and transformation of stem cells.汗腺在人体皮肤中分布广泛，其中外泌汗腺主要起散热排汗作用。汗液分泌由神经系统调控，包括分泌部分泌与导管部重吸收2个过程，涉及钙离子通道、钾离子通道、钠钾氯协同转运蛋白1、Best2蛋白、水通道蛋白5、囊性纤维化跨膜转导调节因子、上皮钠离子通道等多种离子通道和蛋白。该文将对涉及外泌汗腺汗液分泌的神经传导体系、各类离子通道等进行综述，以期为损伤汗腺再生修复及干细胞转化研究提供一定的理论依据。.

Aims The volume of ambulatory total hip arthroplasty (THA) procedures is increasing due to the emphasis on value-based care. The purpose of the study is to identify the causes for failed same-day discharge (SDD) and perioperative factors leading to failed SDD. Methods This retrospective cohort study followed pre-selected patients for SDD THA from 1 August 2018 to 31 December 2020. Inclusion criteria were patients undergoing unilateral THA with appropriate social support, age 18 to 75 years, and BMI < 37 kg/m2. Patients with opioid dependence, coronary artery disease, and valvular heart disease were excluded. Demographics, comorbidities, and perioperative data were collected from the electronic medical records. Possible risk factors for failed SDD were identified using multivariate logistic regression. Results In all, 278 patients were identified with a mean age of 57.1 years (SD 8.1) and a mean BMI of 27.3 kg/m2 (SD 4.5). A total of 96 patients failed SDD, with the most common reasons being failure to clear physical therapy (26%), dizziness (22%), and postoperative nausea and vomiting (11%). Risk factors associated with failed SDD included smokers (odds ratio (OR) 6.24; p = 0.009), a maximum postoperative pain score > 8 (OR 4.76; p = 0.004), and procedures starting after 11 am (OR 2.28; p = 0.015). A higher postoperative tolerable pain goal (numerical rating scale 4 to 10) was found to be associated with successful SDD (OR 2.7; p = 0.001). Age, BMI, surgical approach, American Society of Anesthesiologists grade, and anaesthesia type were not associated with failed SDD. Conclusion SDD is a safe and viable option for pre-selected patients interested in rapid recovery THA. The most common causes for failure to launch were failing to clear physical thereapy and patient symptomatology. Risk factors associated with failed SSD highlight the importance of preoperative counselling regarding smoking cessation and postoperative pain to set reasonable expectations. Future interventions should aim to improve patient postoperative mobilization, pain control, and decrease symptomatology. Cite this article: Bone Jt Open 2022;3(9):684–691.

Introduction Although one of the touted benefits of the direct anterior approach (DAA) includes decreased postoperative pain, there is no consensus on the effect of surgical approach on postoperative pain and subsequent analgesic consumption. Methods Consecutive patients undergoing total hip arthroplasty by a single surgeon from May 2016 to March 2020 were identified. Procedures were categorized as DAA or posterior approach. Patient demographics and surgical details were assessed. Patient-reported maximum pain by postoperative day (POD), total opioid consumption during hospitalization, and whether the patient required a refill of opioid prescription within 3 months after discharge were compared between the two surgical approaches through multivariate analyses. Results A total of 611 patients were included in this study (447 DAA and 164 posterior approaches). On multivariate analyses that controlled for preoperative/intraoperative differences, patients in the DAA group had lower average maximum reported pain (0 to 10 scale) on POD #0 (6.5 versus 6.8, P = 0.034) and POD #1 (5.4 versus 6.1, P = 0.018). However, the DAA was not associated with a statistically significant reduction in total inpatient oral morphine equivalents consumed (79.8 versus 100.1, P = 0.486). Furthermore, there was no association between surgical approach and opioid prescription refill within 3 months after discharge (P = 0.864). Discussion The DAA was associated with slightly lower patient-reported pain. Furthermore, statistical analysis did not provide the necessary evidence to reject the null hypothesis, which was that there would be no difference in opioid utilization between the two approaches. Other perioperative factors may be more important to opioid use reduction than the surgical approach alone.

ObjectiveAnti-drug antibodies (ADA) to anti-tumour necrosis factor (anti-TNF) therapy drive treatment loss of response. An association between intestinal microbial composition and response to anti-TNF therapy was noted. We therefore aimed to assess the implications of antibiotic treatments on ADA formation in patients with inflammatory bowel disease (IBD).DesignWe analysed data from the epi-IIRN (epidemiology group of the Israeli IBD research nucleus), a nationwide registry of all patients with IBD in Israel. We included all patients treated with anti-TNF who had available ADA levels. Survival analysis with drug use as time varying covariates were used to assess the association between antibiotic use and ADA development. Next, specific pathogen and germ-free C57BL mice were treated with respective antibiotics and challenged with infliximab. ADA were assessed after 14 days.ResultsAmong 1946 eligible patients, with a median follow-up of 651 days from initiation of therapy, 363 had positive ADA. Cox proportional hazard model demonstrated an increased risk of ADA development in patients who used cephalosporins (HR=1.97, 95% CI 1.58 to 2.44), or penicillins with β-lactamase inhibitors (penicillin-BLI, HR=1.4, 95% CI 1.13 to 1.74), whereas a reduced risk was noted in patients treated with macrolides (HR=0.38, 95% CI 0.16 to 0.86) or fluoroquinolones (HR=0.20, 95% CI 0.12 to 0.35). In mice exposed to infliximab, significantly increased ADA production was observed in cephalosporin as compared with macrolide pretreated mice. Germ-free mice produced no ADA.ConclusionADA production is associated with the microbial composition. The risk of ADA development during anti-TNF therapy can possibly be reduced by avoidance of cephalosporins and penicillin-BLIs, or by treatment with fluoroquinolones or macrolides.