bluuebunny/crossref_metadata_2025 huggingface dataset:
Apparent total tract macronutrient digestibility of mildly cooked human-grade vegan dog foods and their effects on the blood metabolites and fecal characteristics, microbiota, and metabolites of adult dogs
Authors: Roberts Leah J , Oba Patricia M , Swanson Kelly S
Published: March 2023

Vegan, mildly cooked, and human-grade dog foods are becoming more popular, as beliefs and views of pet owners change. To our knowledge, however, dog studies have not examined the digestibility of commercial vegan diets. Therefore, the objective of this study was to determine the apparent total tract digestibility (ATTD) of mildly cooked human-grade vegan dog foods and their effects on blood metabolites and fecal microbiota, characteristics, and metabolites of adult dogs consuming them. Three commercial dog foods were tested. Two were mildly cooked human-grade vegan dog diets, while the third was a chicken-based extruded dog diet. Twelve healthy adult female beagles (7.81 ± 0.65 kg; 7.73 ± 1.65 yr) were used in a replicated 3 × 3 Latin Square design. The study consisted of three experimental periods, with each composed of a 7 d diet adaptation phase, 15 d of consuming 100% of the diet, a 5 d phase for fecal collection for ATTD measurement, and 1 d for blood collection for serum chemistry and hematology. During the fecal collection period, a fresh sample was collected for fecal scoring and dry matter, pH, metabolite, and microbiota measurements. All data were analyzed using the Mixed Models procedure of SAS (version 9.4). All three diets were shown to be highly digestible, with all macronutrients having digestibility values above 80%. The vegan diets had higher (P < 0.001) ATTD of fat, but lower (P < 0.05) ATTD of organic matter than the extruded diet. Dogs consuming the vegan diets had lower circulating cholesterol (P < 0.001), triglyceride (P < 0.001), and platelet (P < 0.009) concentrations and lower (P < 0.010) blood neutrophil percentages than dogs consuming the extruded diet. Dogs consuming vegan diets had lower (P < 0.001) fecal dry matter percentages, lower (P < 0.001) fecal phenol and indole concentrations, and higher (P = 0.05) fecal short-chain fatty acid concentrations than those consuming the extruded diet. Fecal bacterial alpha and beta diversities were not different (P > 0.05) among diets, but dogs consuming vegan diets had altered (P < 0.05) relative abundances of nearly 20 bacterial genera when compared with those consuming the extruded diet. In conclusion, the mildly cooked human-grade vegan dog foods tested in this study performed well, resulting in desirable fecal characteristics, ATTD, and serum chemistries. The vegan diets tested also led to positive changes to serum lipids and fecal metabolites, and interesting changes to the fecal microbial community.
“Type D” killer whale genomes reveal long-term small population size and low genetic diversity
Authors: Foote Andrew D , Alexander Alana , Ballance Lisa T , Constantine Rochelle , Galletti Vernazzani Muñoz Bárbara , Guinet Christophe , Robertson Kelly M , Sinding Mikkel-Holger S , Sironi Mariano , Tixier Paul , Totterdell John , Towers Jared R , Wellard Rebecca , Pitman Robert L , Morin Phillip A
Published: March 2023

Genome sequences can reveal the extent of inbreeding in small populations. Here, we present the first genomic characterization of type D killer whales, a distinctive eco/morphotype with a circumpolar, subantarctic distribution. Effective population size is the lowest estimated from any killer whale genome and indicates a severe population bottleneck. Consequently, type D genomes show among the highest level of inbreeding reported for any mammalian species (FROH ≥ 0.65). Detected recombination cross-over events of different haplotypes are up to an order of magnitude rarer than in other killer whale genomes studied to date. Comparison of genomic data from a museum specimen of a type D killer whale that stranded in New Zealand in 1955, with 3 modern genomes from the Cape Horn area, reveals high covariance and identity-by-state of alleles, suggesting these genomic characteristics and demographic history are shared among geographically dispersed social groups within this morphotype. Limitations to the insights gained in this study stem from the nonindependence of the 3 closely related modern genomes, the recent coalescence time of most variation within the genomes, and the nonequilibrium population history which violates the assumptions of many model-based methods. Long-range linkage disequilibrium and extensive runs of homozygosity found in type D genomes provide the potential basis for both the distinctive morphology, and the coupling of genetic barriers to gene flow with other killer whale populations.
The Aftermath of Dutch International Crimes Cases
Authors: Bolhuis Maarten P , van Wijk Joris
Published: March 2023

This article describes the scale and nature of international crimes prosecutions in the Netherlands and maps the different scenarios that (may) unfold when criminal proceedings against a migrant suspect of international crimes conclude after acquittal or completion of a sentence. The article is based on an analysis of academic literature, Dutch legislation and case law, policy documents, and media reports. Since 1997, 20 individuals have been prosecuted for international crimes in the Netherlands, 16 of whom were naturalized or dual Dutch citizens, or non-citizens. The article concludes that while the Dutch ‘No Safe Haven’ policy — which we propose consists of a four-pillar model covering criminal law, extradition law, immigration/refugee law, and nationality law — has the potential to reduce impunity for international crimes, it likely results in undesirable, unremovable, and unaccounted for individuals.
Estimating Risk in Illiquid Markets: A Model of Market Friction with Stochastic Volatility
Authors: Buccheri Giuseppe , Grassi Stefano , Vocalelli Giorgio
Published: March 2023

This article deals with the problem of estimating the volatility of a financial security in a market with frictions. We propose a microstructural model with time-varying fundamental price volatility in which the trading price varies only if the value of the information signal is large enough to guarantee a profit in excess of transaction costs. Using transaction data only, the proposed approach allows to recover: (i) the conditional volatility of the information signal, which is thus cleaned out by market frictions and (ii) an estimate of transaction costs. Our analysis reveals that, after correcting for frictions, the risk of illiquid securities is substantially different from what is predicted by traditional volatility models. Furthermore, using a big dataset of intraday returns, we show that our transaction cost estimate is highly correlated with the main illiquidity measures and that such correlations are significant under different volatility regimes.
Endogenous Volatility in the Foreign Exchange Market
Authors: Bargigli Leonardo , Cifarelli Giulio
Published: March 2023

We study two sources of heteroscedasticity in high-frequency financial data and estimate their contribution to overall volatility by means of a Markov switching (MS) structural VAR model. We achieve identification for all coefficients by assuming that the structural errors follow a GARCH-DCC process. Using transaction data of the EUR/USD interdealer market in 2016, we first detect three regimesof volatility. Then we show that both sources of volatility matter for the transmission of shocks, and that information is channeled to the market mostly through demand shocks. This suggests that, on the EUR/USD market, some liquidity takers (LTs) are better informed than both liquidity providers and those LTs who follow a feedback strategy.
Travel-associated melioidosis: a narrative review
Authors: Norman Francesca F , Chen Lin H
Published: March 2023

Background

Melioidosis, caused by Burkholderia pseudomallei, may be considered a neglected tropical disease that remains underdiagnosed in many geographical areas. Travellers can act as the sentinels of disease activity, and data from imported cases may help complete the global map of melioidosis.

Methods

A literature search for imported melioidosis for the period 2016–22 was performed in PubMed and Google Scholar.

Results

In total, 137 reports of melioidosis associated with travel were identified. The majority were males (71%) and associated with exposure in Asia (77%) (mainly Thailand, 41%, and India, 9%). A minority acquired the infection in the Americas–Caribbean area (6%), Africa (5%) and Oceania (2%). The most frequent comorbidity was diabetes mellitus (25%) followed by underlying pulmonary, liver or renal disease (8, 5 and 3%, respectively). Alcohol/tobacco use were noted for seven and six patients, respectively (5%). Five patients (4%) had associated non-human immunodeficiency virus (HIV)-related immunosuppression, and three patients (2%) had HIV infection. One patient (0.8%) had concomitant coronavirus disease 19. A proportion (27%) had no underlying diseases. The most frequent clinical presentations included pneumonia (35%), sepsis (30%) and skin/soft tissue infections (14%). Most developed symptoms <1 week after return (55%), and 29% developed symptoms >12 weeks after. Ceftazidime and meropenem were the main treatments used during the intensive intravenous phase (52 and 41% of patients, respectively) and the majority (82%) received co-trimoxazole alone/combination, for the eradication phase. Most patients had a favourable outcome/survived (87%). The search also retrieved cases in imported animals or cases secondary to imported commercial products.

Conclusions

As post-pandemic travel soars, health professionals should be aware of the possibility of imported melioidosis with its diverse presentations. Currently, no licensed vaccine is available, so prevention in travellers should focus on protective measures (avoiding contact with soil/stagnant water in endemic areas). Biological samples from suspected cases require processing in biosafety level 3 facilities.
Breast Tumor Cells Evade the Cytotoxic Action of Anastrozole, Aspirin, and Clopidogrel Cocktail
Authors: Arnachellen Derushka , Xulu Kutlwano R , Pillay Kiveshen , Augustine Tanya N
Published: March 2023

Globally, breast cancer is among the most frequently diagnosed and common cause of death among women. Aromatase inhibitors, such as anastrozole, are one of the first-line therapies used in the treatment of breast cancer in postmenopausal women; however, thromboembolic complications are common. Thus, this study investigated the combined effects of anastrozole and antiplatelet therapies, aspirin and clopidogrel, on breast cancer cytotoxicity and survival in vitro. Breast cancer cell lines (MCF-7 and T47D) were treated with varying Cmax concentrations of anastrozole and/or antiplatelet therapies for 24 h. A wound-healing scratch assay was used to measure migration and the WST-1 assay for cellular proliferation. An autophagy/cytotoxicity dual staining kit was used to assay cell death and survival. Changes in cell morphology were assessed using scanning electron microscopy. Data were analyzed with Statistica software. Our findings showed that sub-phenotypic differences exist between the luminal-A breast cancer cell lines, with T47D cells being more aggressive than MCF-7 cells. Cellular proliferation and migration responded in a dose-dependent manner for the different treatment groups. Notably, anastrozole combined with aspirin and clopidogrel mediated higher levels of cell survival than each agent individually, with autophagy levels being significantly increased in comparison to that induced with antiplatelet therapy alone.
Rhapsody-Csimulations – anisotropic thermal conduction, black hole physics, and the robustness of massive galaxy cluster scaling relations
Authors: Pellissier Alisson , Hahn Oliver , Ferrari Chiara
Published: March 2023

We present the Rhapsody-C simulations that extend the Rhapsody-G suite of massive galaxy clusters at the $M_{\rm vir}\sim 10^{15}\, {\rm M}_{\odot }$ scale with cosmological magneto-hydrodynamic zoom-in simulations that include anisotropic thermal conduction, modified supermassive black hole (SMBH) feedback, new SMBH seeding, and the SMBH orbital decay model. These modelling improvements have a dramatic effect on the SMBH growth, star formation, and gas depletion in the proto-clusters. We explore the parameter space of the models and report their effect on both star formation and the thermodynamics of the intracluster medium (ICM) as observed in X-ray and SZ observations. We report that the star formation in proto-clusters is strongly impacted by the choice of the SMBH seeding as well as the orbital decay of SMBHs. The feedback from AGNs is substantially boosted by the SMBH decay; its time evolution and impact range differ noticeably depending on the AGN energy injection scheme used. Compared to a mass-weighted injection whose energy remains confined close to the central SMBHs, a volume-weighted thermal energy deposition allows to heat the ICM out to large radii that severely quenches the star formation in proto-clusters. By flattening out temperature gradients in the ICM, anisotropic thermal conduction can reduce star formation early on but weakens and delays the AGN activity. Despite the dissimilarities found in the stellar and gaseous content of our haloes, the cluster scaling relations we report are surprisingly insensitive to the subresolution models used and are in good agreement with recent observational and numerical studies.
Gradual increase of avacopan dose with concomitant ursodeoxycholic acid use may help avoid the risk of C5a receptor inhibitor-induced liver injury in antineutrophil cytoplasmic antibody-associated vasculitis
Authors: Kataoka Hiroshi , Tomita Tomoko , Nakanowatari Mika , Kondo Makoto , Mukai Masaya
Published: March 2023

Microscopic polyangiitis is a necrotising vasculitis characterised by anti-neutrophil cytoplasmic antibodies against myeloperoxidase. The complement component 5a receptor inhibitor avacopan effectively sustains remission in microscopic polyangiitis with a reduction in prednisolone dosage. Liver damage is a safety concern for this drug. However, when it occurs and how to treat it remain unknown. A 75-year-old man developed microscopic polyangiitis and presented with hearing impairment and proteinuria. Methylprednisolone pulse therapy followed by 30 mg/day prednisolone and two doses of weekly rituximab were administered. Avacopan was initiated to taper prednisolone for sustained remission. After 9 weeks, liver dysfunction and sparse skin eruptions developed. The cessation of avacopan and the initiation of ursodeoxycholic acid improved liver function without discontinuation of prednisolone and other concomitant drugs. After 3 weeks, avacopan was rechallenged with a small dose that was gradually increased; ursodeoxycholic acid was continued. Full-dose avacopan did not induce recurrence of liver injury. Therefore, gradually increasing the dose of avacopan with concomitant ursodeoxycholic acid use may help avoid possible avacopan-induced liver injury.
Overcoming translational barriers in H3K27-altered diffuse midline glioma: Increasing the drug-tumor residence time
Authors: Power Erica A , Rechberger Julian S , Zhang Liang , Oh Ju-Hee , Anderson Jacob B , Nesvick Cody L , Ge Jizhi , Hinchcliffe Edward H , Elmquist William F , Daniels David J
Published: March 2023

Background

H3K27-altered diffuse midline glioma (DMG) is the deadliest pediatric brain tumor; despite intensive research efforts, every clinical trial to date has failed. Is this because we are choosing the wrong drugs? Or are drug delivery and other pharmacokinetic variables at play? We hypothesize that the answer is likely a combination, where optimization may result in a much needed novel therapeutic approach.

Methods

We used in vitro drug screening, patient samples, and shRNA knockdown models to identify an upregulated target in DMG. A single small molecule protein kinase inhibitor with translational potential was selected for systemic and direct, loco-regional delivery to patient-derived xenografts (PDX) and genetically engineered mouse models (GEMM). Pharmacokinetic studies were conducted in non-tumor bearing rats.

Results

Aurora kinase (AK) inhibitors demonstrated strong antitumor effects in DMG drug screens. Additional in vitro studies corroborated the importance of AK to DMG survival. Systemic delivery of alisertib showed promise in subcutaneous PDX but not intracranial GEMM and PDX models. Repeated loco-regional drug administration into the tumor through convection-enhanced delivery (CED) was equally inefficacious, and pharmacokinetic studies revealed rapid clearance of alisertib from the brain. In an effort to increase the drug to tumor residence time, continuous CED over 7 days improved drug retention in the rodent brainstem and significantly extended survival in both orthotopic PDXs and GEMMs.

Conclusions

These studies provide evidence for increasing drug-tumor residence time of promising targeted therapies via extended CED as a valuable treatment strategy for DMG.
Revisiting Androgen Receptor Signaling in Breast Cancer
Authors: Dai Charles , Ellisen Leif W
Published: March 2023

Aberrant estrogen receptor (ER) signaling is central to the pathogenesis of many breast cancers. Like ER, the androgen receptor (AR) is a steroid nuclear receptor that is frequently expressed in breast cancer and has long been considered an attractive therapeutic target. Although androgens were historically employed in the treatment of breast cancer, this strategy has largely fallen out of favor with the advent of modern anti-­estrogens, due to virilizing effects from androgens, as well as concerns that androgens could be converted to estrogens to fuel tumor growth. Recent molecular advances, however, including the development of selective androgen receptor modulators, have renewed interest in targeting the AR. Yet androgen signaling in breast cancer remains incompletely understood, and preclinical studies have yielded conflicting and sometimes contradictory evidence regarding the role of AR, resulting in clinical investigations into both AR agonists and antagonists. It is increasingly recognized that AR may very well be context-specific, with divergent actions in ER-positive versus ER-negative disease. Here, we will summarize our current understanding of AR biology and insights from recent investigations into AR–directed therapies in breast cancer.
Patient Characteristics Associated With Chemotherapy-Induced Peripheral Neuropathy Severity in a Phase II Clinical Trial: A Retrospective Analysis
Authors: Zhi Wanqing Iris , Dreyfus Nechama , Lessing Alexie , Galantino Marylou , Piulson Lauren , Kot Kevin Liu , Li Susan , Bao Ting
Published: March 2023

Introduction

Chemotherapy-induced peripheral neuropathy (CIPN) can lead to chemotherapy dose reduction, delay, and discontinuation, and has limited effective prevention strategies. Our study aimed to identify patient characteristics associated with CIPN severity during weekly paclitaxel chemotherapy in people with early-stage breast cancer.

Methods

We retrospectively collected baseline data including participants’ age, gender, race, body mass index (BMI), hemoglobin (regular and A1C), thyroid stimulating hormone, Vitamins (B6, B12, and D), anxiety, and depression up to 4 months prior to their first paclitaxel treatment. We also collected CIPN severity by Common Terminology Criteria for Adverse Events (CTCAE) after chemotherapy, chemotherapy relative dose density (RDI), disease recurrence, and mortality rate at the time of the analysis. Logistic regression was used for statistical analysis.

Results

We extracted 105 participants’ baseline characteristics from electronic medical records. Baseline BMI was associated with CIPN severity (Odds Ratio [OR] 1.08; 95% CI, 1.01-1.16, P = .024). No significant correlations were observed in other covariates. At median follow-up (61 months), there were 12 (9.5%) breast cancer recurrences and six (5.7%) breast cancer-related deaths. Higher chemotherapy RDI was associated with improved disease-free survival (DFS, OR 1.025; 95% CI, 1.00-1.05; P = .028).

Conclusions and Relevance

Baseline BMI may be a risk factor for CIPN and suboptimal chemotherapy delivery due to CIPN may negatively impact disease-free survival in patients with breast cancer. Further study is warranted to identify mitigating lifestyle factors to reduce incidences of CIPN during breast cancer treatment.
Acupuncture May Help to Prevent Chemotherapy-Induced Peripheral Neuropathy: A Randomized, Sham-Controlled, Single-Blind Study
Authors: Huang Ming-Cheng , Chang Sheng-Chi , Liao Wen-Ling , Ke Tao-Wei , Lee Ai-Lin , Wang Hwei-Ming , Chang Che-Pin , Yen Hung-Rong , Chang Hen-Hong , Chen William Tzu-Liang
Published: March 2023

Objective

This study investigated the efficacy of acupuncture in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients with colorectal cancer (CRC).

Methods

This single center, randomized, controlled, single-blind clinical trial randomly assigned patients with stage 3 CRC attending outpatient clinics in China Medical University Hospital to either verum or sham acupuncture treatment concurrently with chemotherapy. Primary outcomes were nerve conduction velocity (NCV) and touch thresholds of limb terminals. Secondary outcomes were total and subdomain scores on the Functional Assessment of Cancer Therapy-General (FACT-G), and scores on the FACT/GOG-Ntx subscale and the Brief Pain Inventory-Short Form (BPI-SF), at baseline, weeks 12, 36, and follow-up (week 48).

Results

Thirty-two patients met the inclusion criteria and received verum acupuncture (N = 16) or sham acupuncture (N = 16). Under the ­intent-to-treat principle, 26 participants were analyzed. Significant changes from baseline for questionnaire scores and sensory NCV were observed in both study groups. Sham acupuncture was associated with significant reductions from baseline in motor NCV and sensory touch thresholds; no such changes were observed with verum acupuncture. No serious adverse events were reported.

Conclusion

Prophylactic acupuncture may exert neuroprotective effects on mechanical or tactile touch thresholds during chemotherapy regimens in patients with CRC, with evidence of this protectiveness persisting at 6 months’ follow-up. The lack of change in motor NCV values with verum acupuncture indicates neuroprotective effects. Sensory NCV values and patient-reported outcomes did not differ significantly between the study groups.
HER2 Expression Associated with Clinical Characteristics and Prognosis of Urothelial Carcinoma in a Chinese Population
Authors: Zhou Li , Shao Zhiting , Liu Yiqiang , Yan Xieqiao , Li Juan , Wu Xiaowen , Tang Bixia , Li Siming , Cui Chuanliang , Chi Zhihong , Si Lu , Kong Yan , Mao Lili , Lian Bin , Wang Xuan , Bai Xue , Dai Jie , Guo Jun , Sheng Xinan
Published: March 2023

Background

The frequency of HER2 overexpression in bladder cancer is reported as 9%-61%. HER2 alteration correlates with aggressive disease in bladder cancer. Traditional anti-HER2 targeted therapy has failed to show clinical benefits in patients with advanced urothelial carcinoma .

Methods

The information on pathologically proven patients with urothelial carcinoma with detected HER2 status was collected from the database of Peking University Cancer Hospital. The HER2 expression, as well as its association with clinical characteristics and prognosis, was analyzed.

Results

A total of 284 consecutive patients with urothelial carcinoma were enrolled. HER2 was positive (IHC 2+/3+) in 44% of urothelial carcinoma. HER2 positivity was found more frequent in UCB than in UTUC (51% vs. 38%). Stage, radical surgery, and histological variant were associated with survival (P < .05). For metastatic patients, multivariate analysis shows that 3 indicators, including liver metastasis, the number of involved organs, and anemia, are independent risk factors of prognosis. Receiving immunotherapy or disitamab vedotin (DV) treatment is an independent protecting factor. The survival of patients with low HER2 expression was also significantly improved by the treatment of DV (P < .001). HER2 expression (IHC 1+, 2+, 3+) was associated with a better prognosis in this population.

Conclusion

DV has improved the survival of patients with urothelial carcinoma in the real world. With the new-generation anti-HER2 ADC treatment, HER2 expression is no longer a poor prognostic factor.
Efficacy and Safety of Adjuvant Radiotherapy in Re-excised Soft-tissue Sarcoma After Unplanned Resection
Authors: Allignet Benoît , Pou Paul , Izarn Floriane , Ray-Coquard Isabelle , Blay Jean-Yves , Dufresne Armelle , Brahmi Mehdi , Bouhamama Amine , Meeus Pierre , Vaz Gualter , Gouin Francois , Meurgey Alexandra , Karanian Marie , Moncharmont Coralie , Waissi Waisse , Sunyach Marie-Pierre
Published: March 2023

Introduction

The objective of this study was to evaluate the efficacy and safety of adjuvant radiotherapy (aRT) in patients with soft-tissue sarcoma (STS) re-excised after unplanned tumor resection (UPR).

Materials and Methods

From 2000 to 2015, we retrospectively evaluated patients with STS of limb or trunk who underwent post-UPR re-excision in our expert center and received or not aRT.

Results

Median follow-up was 121 months (IQR 94-165). Among the 145 patients, 37 were not treated with aRT (no-RT) and 108 received aRT with a median radiation dose of 50 Gy (IQR 50-60). At 10 years, patients in the aRT and no-RT groups showed a cumulative incidence of local failure (10y-LF) of 14.7% and 37.7%, and a local recurrence-free survival (10y-LRFS) of 61.3% and 45.8%, respectively. Multivariate analysis identified aRT and age ≥70 years as independent predictors of both LF and LRFS, while grade 3 and deep-seated tumor were independent predictors of LRFS. In overall population, 10-year distant metastasis-free survival (10y-DMFS) and overall survival (10y-OS) were 63.7% and 69.4%. In multivariate analyses, age ≥70 years, grade 3, and deep-seated lesion were associated with shorter DMFS and OS. Acute severe adverse events were not significantly increased in aRT group (14.8% vs. 18.1%, P = .85) but dramatically increased if radiation dose exceeded 50 Gy (risk ratio 2.96 compared to ≤50 Gy, P = .04).

Conclusion

In STS patients re-excised after UPR, 50 Gy aRT was safe and associated with reduced LF and longer LRFS. It seems to be beneficial even in absence of residual disease or in absence of initial adverse prognostic factors.
Protein S-acylation controls the subcellular localization and biological activity of PHYTOCHROME KINASE SUBSTRATE
Authors: Lopez Vazquez Ana , Allenbach Petrolati Laure , Legris Martina , Dessimoz Christophe , Lampugnani Edwin R , Glover Natasha , Fankhauser Christian
Published: March 2023

PHYTOCHROME KINASE SUBSTRATE (PKS) proteins are involved in light-modulated changes in growth orientation. They act downstream of phytochromes to control hypocotyl gravitropism in the light and act early in phototropin signaling. Despite their importance for plant development, little is known about their molecular mode of action, except that they belong to a protein complex comprising phototropins at the plasma membrane (PM). Identifying evolutionary conservation is one approach to revealing biologically important protein motifs. Here, we show that PKS sequences are restricted to seed plants and that these proteins share 6 motifs (A to F from the N to the C terminus). Motifs A and D are also present in BIG GRAIN, while the remaining 4 are specific to PKSs. We provide evidence that motif C is S-acylated on highly conserved cysteines, which mediates the association of PKS proteins with the PM. Motif C is also required for PKS4-mediated phototropism and light-regulated hypocotyl gravitropism. Finally, our data suggest that the mode of PKS4 association with the PM is important for its biological activity. Our work, therefore, identifies conserved cysteines contributing to PM association of PKS proteins and strongly suggests that this is their site of action to modulate environmentally regulated organ positioning.
Do Short Sellers Affect Corporate Innovation? Evidence from a Policy Experiment
Authors: He Jie (Jack) , Ren Xiao (Shaun) , Tian Xuan
Published: March 2023

We examine the effect of short sellers on corporate innovation. To establish causality, we use a policy experiment that exogenously removes the short-selling constraint for a randomly selected subsample of Russell 3000 firms. We find that innovation quality, value, and efficiency of treatment firms improve significantly more than those of control firms surrounding the policy shock. The exposure to patenting-related litigation initiated by short sellers is a plausible underlying mechanism through which short sellers discipline firm managers and enhance innovation. Our paper provides new insights into an unintended real effect of short sellers, specifically their improvement of technological innovation. (JEL G14, G18, G34, K22, O31, O32)
Benzodiazepine, Z-drug, and sleep medication prescriptions in male and female people with opioid use disorder on buprenorphine and comorbid insomnia: an analysis of multistate insurance claims
Authors: Martin Caitlin E , Patel Hetal , Dzierzewski Joseph M , Moeller F Gerard , Bierut Laura J , Grucza Richard A , Xu Kevin Y
Published: March 2023

Study Objectives

In adult populations, women are more likely than men to be prescribed benzodiazepines. However, such disparities have not been investigated in people with opioid use disorder (OUD) and insomnia receiving buprenorphine, a population with particularly high sedative/hypnotic receipt. This retrospective cohort study used administrative claims data from Merative MarketScan Commercial and MultiState Medicaid Databases (2006–2016) to investigate sex differences in the receipt of insomnia medication prescriptions among patients in OUD treatment with buprenorphine.

Methods

We included people aged 12–64 years with diagnoses of insomnia and OUD-initiating buprenorphine during the study timeframe. The predictor variable was sex (female versus male). The primary outcome was receipt of insomnia medication prescription within 60 days of buprenorphine start, encompassing benzodiazepines, Z-drugs, or non-sedative/hypnotic insomnia medications (e.g. hydroxyzine, trazodone, and mirtazapine). Associations between sex and benzodiazepine, Z-drug, and other insomnia medication prescription receipt were estimated using Poisson regression models.

Results

Our sample included 9510 individuals (female n = 4637; male n = 4873) initiating buprenorphine for OUD who also had insomnia, of whom 6569 (69.1%) received benzodiazepines, 3891 (40.9%) Z-drugs, and 8441 (88.8%) non-sedative/hypnotic medications. Poisson regression models, adjusting for sex differences in psychiatric comorbidities, found female sex to be associated with a slightly increased likelihood of prescription receipt: benzodiazepines (risk ratio [RR], RR = 1.17 [1.11–1.23]), Z-drugs (RR = 1.26 [1.18–1.34]), and non-sedative/hypnotic insomnia medication (RR = 1.07, [1.02–1.12]).

Conclusions

Sleep medications are commonly being prescribed to individuals with insomnia in OUD treatment with buprenorphine, with sex-based disparities indicating a higher prescribing impact among female than male OUD treatment patients.
“We’re Better than Most”: Diversity Discourse in the San Francisco Bay Area Tech Industry
Authors: Luhr Sigrid
Published: March 2023

Despite recent efforts to diversify their workplaces, tech companies remain predominantly White, Asian, and male—drawing on in-depth interviews with 50 tech workers in the San Francisco Bay Area, this article examines how these workers think about the term “diversity” with respect to their own companies. While previous research on diversity within organizations largely centers on Human Resource professionals or policy makers, this article unpacks how workers themselves define and discuss diversity. Although most respondents acknowledged a “diversity problem” in the tech industry, they saw their own companies as “better than most.” They made this claim by 1) drawing relative comparisons with other tech companies; 2) citing evidence of efforts their companies were making to increase diversity; and 3) using expansive definitions of the term “diversity.” Yet perceiving their companies as “better than most” may breed a kind of complacency where workers consider their companies “above average” on diversity when they look similar to other companies. These interviews provide evidence that the diversity initiatives at tech companies – while not necessarily effective in reducing racial or gender inequality – are effective in convincing some workers that their companies are diverse. This article provides insight into why efforts to increase diversity within organizations may stall.
Mesenchymal Stromal Cells Suppress T-Cell-Mediated Delayed-Type Hypersensitivity via ALCAM-CD6 Interaction
Authors: Cho WonKyung J , Mittal Sharad K , Chauhan Sunil K
Published: March 2023

Mounting evidence suggests mesenchymal stromal cells (MSCs) suppress CD4+ T-cell activation, but whether MSCs directly regulate activation and expansion of allogeneic T cells has not been fully deciphered. Here, we identified that both human and murine MSCs constitutively express ALCAM, a cognate ligand for CD6 receptors on T cells, and investigated its immunomodulatory function using in vivo and in vitro experiments. Our controlled coculture assays demonstrated that ALCAM-CD6 pathway is critical for MSCs to exert its suppressive function on early CD4+CD25− T-cell activation. Moreover, neutralizing ALCAM or CD6 results in the abrogation of MSC-mediated suppression of T-cell expansion. Using a murine model of delayed-type hypersensitivity response to alloantigen, we show that ALCAM-silenced MSCs lose the capacity to suppress the generation of alloreactive IFNγ-secreting T cells. Consequently, MSCs, following ALCAM knockdown, failed to prevent allosensitization and alloreactive T-cell-mediated tissue damage.
SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction
Authors: Wilkes Mark C , Chae Hee-Don , Scanlon Vanessa , Cepika Alma-Martina , Wentworth Ethan P , Saxena Mallika , Eskin Ascia , Chen Zugen , Glader Bert , Grazia Roncarolo Maria , Nelson Stanley F , Sakamoto Kathleen M
Published: March 2023

Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome associated with severe anemia, congenital malformations, and an increased risk of developing cancer. The chromatin-binding special AT-rich sequence-binding protein-1 (SATB1) is downregulated in megakaryocyte/erythroid progenitors (MEPs) in patients and cell models of DBA, leading to a reduction in MEP expansion. Here we demonstrate that SATB1 expression is required for the upregulation of the critical erythroid factors heat shock protein 70 (HSP70) and GATA1 which accompanies MEP differentiation. SATB1 binding to specific sites surrounding the HSP70 genes promotes chromatin loops that are required for the induction of HSP70, which, in turn, promotes GATA1 induction. This demonstrates that SATB1, although gradually downregulated during myelopoiesis, maintains a biological function in early myeloid progenitors.
Performance Assessment of the American College of Surgeons Risk Calculator in Metastatic Spinal Tumor Surgery
Authors: Ryvlin Jessica , Hamad Mousa K. , Wang Benjamin , Xavier Jorden , De la Garza Ramos Rafael , Murthy Saikiran G. , Gelfand Yaroslav , Yassari Reza
Published: March 2023

Study Design.

This was a retrospective cohort study.

Objective.

The objective of this study was to assess the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) surgical risk calculator performance in patients undergoing surgery for metastatic spine disease.

Summary of Background Data.

Patients with spinal metastases may require surgical intervention for cord compression or mechanical instability. The ACS-NSQIP calculator was developed to assist surgeons with estimating 30-day postoperative complications based on patient-specific risk factors and has been validated within several surgical patient populations.

Materials and Methods.

We included 148 consecutive patients at our institution who underwent surgery for metastatic spine disease between 2012 and 2022. Our outcomes were 30-day mortality, 30-day major complications, and length of hospital stay (LOS). Predicted risk, determined by the calculator, was compared with observed outcomes using receiver operating characteristic curves with area under the curve (AUC) and Wilcoxon signed-rank tests. Analyses were repeated using individual corpectomy and laminectomy Current Procedural Terminology (CPT) codes to determine procedure-specific accuracy.

Results.

Based on the ACS-NSQIP calculator, there was good discrimination between observed and predicted 30-day mortality incidence overall (AUC=0.749), as well as in corpectomy cases (AUC=0.745) and laminectomy cases (AUC=0.788). Poor 30-day major complication discrimination was seen in all procedural cohorts, including overall (AUC=0.570), corpectomy (AUC=0.555), and laminectomy (AUC=0.623). The overall median observed LOS was similar to predicted LOS (9 vs. 8.5 d, P=0.125). Observed and predicted LOS were also similar in corpectomy cases (8 vs. 9 d; P=0.937) but not in laminectomy cases (10 vs. 7 d, P=0.012).

Conclusions.

The ACS-NSQIP risk calculator was found to accurately predict 30-day postoperative mortality but not 30-day major complications. The calculator was also accurate in predicting LOS following corpectomy but not laminectomy. While this tool may be utilized to predict risk short-term mortality in this population, its clinical value for other outcomes is limited.
Patient-Centered Outcomes Following Prone Lateral Single-Position Approach to Same-Day Circumferential Spine Surgery
Authors: Passias Peter G. , Williamson Tyler K. , Krol Oscar , Joujon-Roche Rachel , Imbo Bailey , Tretiakov Peter , Ahmad Salman , Bennett-Caso Claudia , Lebovic Jordan , Owusu-Sarpong Stephane , Park Paul , Chou Dean , Vira Shaleen , Diebo Bassel G. , Schoenfeld Andrew J.
Published: March 2023

Study Design.

Retrospective study

Objective.

Evaluate surgical characteristics and postoperative 2-year results of the PL approach to spinal fusion

Summary of Background Data.

Prone-lateral(PL) single positioning has recently gained popularity in spine surgery due to lower blood loss and operative time, but has yet to be examined for other notable outcomes, including realignment and patient-reported measures.

Methods.

We included circumferential spine fusion patients with minimum one-year follow-up. Patients stratified into groups based on undergoing PL approach versus same-day staged(Staged). Means comparison tests identified differences in baseline parameters. Multivariable logistic regression, controlling for age, levels fused, and Charlson Comorbidity Index(CCI) was used to determine the influence of approach on complication rates, radiographic and patient-reported outcomes up to two years.

Results.

122 patients were included. 72(59%) same-day staged and 50(41%) PL. PL patients were older with lower BMI(both P<0.05). Patients undergoing PL procedures had lower EBL and operative time(both P<0.001), along with fewer osteotomies(63% vs. 91%,P<0.001). This translated to shorter length of stay(3.8 d vs. 4.9,P=0.041). PL procedures demonstrated better correction in both PT(4.0 vs. −0.2,P=0.033 and PI-LL(−3.7 vs. 3.1,P=0.012). PL procedures were more likely to improve in GAP relative pelvic version(OR: 2.3,[1.5-8.8];P=0.003]. PL patients suffered less complications during the perioperative period and greater improvement in NRS-Back(−6.0 vs. −3.3,P=0.031), with less reoperations(0.0% vs. 4.8%,P=0.040) by two years.

Conclusions.

Patients undergoing prone lateral single position procedures received less invasive procedures with better correction of pelvic compensation, as well as earlier discharge. The prone lateral cohort also demonstrated greater clinical improvement and lower rate of reoperations by two years following spinal corrective surgery.

Level of Evidence.

III
Limiting Dynamic Driving Pressure in Patients Requiring Mechanical Ventilation*
Authors: Urner Martin , Jüni Peter , Rojas-Saunero L. Paloma , Hansen Bettina , Brochard Laurent J. , Ferguson Niall D. , Fan Eddy
Published: March 2023

Objectives:

Previous studies reported an association between higher driving pressure (∆P) and increased mortality for different groups of mechanically ventilated patients. However, it remained unclear if sustained intervention on ∆P, in addition to traditional lung-protective ventilation, improves outcomes. We investigated if ventilation strategies limiting daily static or dynamic ∆P reduce mortality compared with usual care in adult patients requiring greater than or equal to 24 hours of mechanical ventilation.

Design:

For this comparative effectiveness study, we emulated pragmatic clinical trials using data from the Toronto Intensive Care Observational Registry recorded between April 2014 and August 2021. The per-protocol effect of the interventions was estimated using the parametric g-formula, a method that controls for baseline and time-varying confounding, as well as for competing events in the analysis of longitudinal exposures.

Setting:

Nine ICUs from seven University of Toronto-affiliated hospitals.

Patients:

Adult patients (≥18 yr) requiring greater than or equal to 24 hours of mechanical ventilation.

Interventions:

Receipt of a ventilation strategy that limited either daily static or dynamic ∆P less than or equal to 15 cm H2O compared with usual care.

Measurements and Main Results:

Among the 12,865 eligible patients, 4,468 of (35%) were ventilated with dynamic ∆P greater than 15 cm H2O at baseline. Mortality under usual care was 20.1% (95% CI, 19.4–20.9%). Limiting daily dynamic ∆P less than or equal to 15 cm H2O in addition to traditional lung-protective ventilation reduced adherence-adjusted mortality to 18.1% (95% CI, 17.5–18.9%) (risk ratio, 0.90; 95% CI, 0.89–0.92). In further analyses, this effect was most pronounced for early and sustained interventions. Static ∆P at baseline were recorded in only 2,473 patients but similar effects were observed. Conversely, strict interventions on tidal volumes or peak inspiratory pressures, irrespective of ∆P, did not reduce mortality compared with usual care.

Conclusions:

Limiting either static or dynamic ∆P can further reduce the mortality of patients requiring mechanical ventilation.
Implementation of Video Laryngoscope-Assisted Coaching Reduces Adverse Tracheal Intubation-Associated Events in the PICU*
Authors: Giuliano John , Krishna Ashwin , Napolitano Natalie , Panisello Josep , Shenoi Asha , Sanders Ronald C. , Rehder Kyle , Al-Subu Awni , Brown Calvin , Edwards Lauren , Wright Lisa , Pinto Matthew , Harwayne-Gidansky Ilana , Parsons Simon , Romer Amy , Laverriere Elizabeth , Shults Justine , Yamada Nicole K. , Walsh Catharine M. , Nadkarni Vinay , Nishisaki Akira ,   for the National Emergency Airway Registry for Children (NEAR4KIDS) and Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: March 2023

Objectives:

To evaluate implementation of a video laryngoscope (VL) as a coaching device to reduce adverse tracheal intubation associated events (TIAEs).

Design:

Prospective multicenter interventional quality improvement study.

Setting:

Ten PICUs in North America.

Patients:

Patients undergoing tracheal intubation in the PICU.

Interventions:

VLs were implemented as coaching devices with standardized coaching language between 2016 and 2020. Laryngoscopists were encouraged to perform direct laryngoscopy with video images only available in real-time for experienced supervising clinician-coaches.

Measurements and Main Results:

The primary outcome was TIAEs. Secondary outcomes included severe TIAEs, severe hypoxemia (oxygen saturation < 80%), and first attempt success. Of 5,060 tracheal intubations, a VL was used in 3,580 (71%). VL use increased from baseline (29.7%) to implementation phase (89.4%; p < 0.001). VL use was associated with lower TIAEs (VL 336/3,580 [9.4%] vs standard laryngoscope [SL] 215/1,480 [14.5%]; absolute difference, 5.1%; 95% CI, 3.1–7.2%; p < 0.001). VL use was associated with lower severe TIAE rate (VL 3.9% vs SL 5.3%; p = 0.024), but not associated with a reduction in severe hypoxemia (VL 15.7% vs SL 16.4%; p = 0.58). VL use was associated with higher first attempt success (VL 71.8% vs SL 66.6%; p < 0.001). In the primary analysis after adjusting for site clustering, VL use was associated with lower adverse TIAEs (odds ratio [OR], 0.61; 95% CI, 0.46–0.81; p = 0.001). In secondary analyses, VL use was not significantly associated with severe TIAEs (OR, 0.72; 95% CI, 0.44–1.19; p = 0.20), severe hypoxemia (OR, 0.95; 95% CI, 0.73–1.25; p = 0.734), or first attempt success (OR, 1.28; 95% CI, 0.98–1.67; p = 0.073). After further controlling for patient and provider characteristics, VL use was independently associated with a lower TIAE rate (adjusted OR, 0.65; 95% CI, 0.49–0.86; p = 0.003).

Conclusions:

Implementation of VL-assisted coaching achieved a high level of adherence across the PICUs. VL use was associated with reduced adverse TIAEs.
Better renal replacement therapy to improve sexual function in female patients with end-stage renal disease: A cross-sectional study
Authors: Tjahjodjati Tjahjodjati , Steven Steven
Published: March 2023

Background

Sexual dysfunction is commonly observed in patients with end-stage renal disease (ESRD). Sexual dysfunction in correlation with ESRD is associated with physiological and psychological problems resulting in low sexual desire, arousal, difficulties in achieving orgasm, and pain during intercourse. Studies on female sexual dysfunction (FSD) in correlation with renal replacement therapy are limited, and previous studies reporting contradictive results have indicated that the best modality for providing better outcomes (especially on FSD) remains unclear. Thus, this study aimed to compare the sexual function between female patients with ESRD who were on continuous ambulatory peritoneal dialysis (CAPD) and those on hemodialysis (HD).

Materials and methods

This study enrolled female patients who were randomly selected from the urology and renal division of the Internal Medicine Outpatient Clinic of our hospital from January 2020 to August 2021 and divided into the following groups: predialysis, HD, CAPD, and control groups. The participants were asked to fill out the Female Sexual Function Index (FSFI) questionnaires, and their data were recorded and analyzed using GraphPad Prism 9.0.0.

Results

Of the 280 patients, 200 female patients were included in this study. The rate of FSD (cutoff: 26.55) was 42% in the control group, 72% in the predialysis group, 62% in the CAPD group, and 66% the in HD group. The control group had a higher mean score in all parameters (p< 0.05). The total FSFI mean score indicated no significant difference (p> 0.05) between the patients on HD and those on CAPD; the mean of each point was almost identical except for satisfaction, which was higher among patients on CAPD (p< 0.05). Significant differences in the components of desire, arousal, orgasm, and satisfaction were observed between the groups.

Conclusions

Patients on CAPD had better FSFI scores than the female patients with ESRD who were on HD, and the scores of both groups of patients were better than those of the predialysis group.