bluuebunny/crossref_metadata_2025 huggingface dataset:
Ton S 415: a close binary containing an intermediate helium subdwarf discovered with SALT and TESS
Authors: Snowdon E J , Jeffery C S , Schlagenhauf S , Dorsch M , Monageng I M
Published: July 2023

Hot subdwarfs are early-type low-mass stars lying between the main sequence and the white dwarf sequence. The majority have helium-burning cores and helium-poor surfaces. A minority have helium-rich surfaces. A few, including Ton S 415, have surfaces with between 10 per cent and 90  per cent helium (by number). Their properties are diverse and their origins mostly unknown. Ton S 415 was identified as a suspected binary in a Southern African Large Telescope (SALT) survey of hot subdwarfs from its large radial velocity. Using SALT spectroscopy and Transiting Exoplanet Survey Satellite light curves, we confirm that Ton S 415 is a close binary with an orbital period $p=84.6460\pm 0.0004\, {\rm min}$ and velocity semi-amplitude $K=175.5\pm 1.0\, {\rm km\, s^{-1}}$. Analysis of the SALT spectrum and broad-band spectral energy distribution shows the visible star to have an effective temperature $T_{\rm eff}=43\, 300\pm 1000\, {\rm K}$, surface gravity $\log g/{\rm cm\, s^{-2}}=5.89\pm 0.10$, surface helium-to-hydrogen ratio log y = −0.62 ± 0.10, radius $R=0.1074\pm 0.0025\, R_{\odot }$, and mass $M=0.33\pm 0.09\, {\rm {\rm M}_{\odot }}$. By modelling the light curve, we estimate the binary mass ratio to be q = 0.7 ± 0.3 and infer an unseen white dwarf companion with a mass of $M_{\rm WD}=0.47\pm 0.24\, {\rm {\rm M}_{\odot }}$. The results are consistent with a post-common-envelope binary that lost its hydrogen envelope before reaching the peak of the red giant branch, becoming a hot subdwarf with a non-canonical mass. We predict that the system will evolve into a double white dwarf binary before eventually either forming a stably accreting AM CVn system, or merging to form an R CrB star.
The energy distribution of the first supernovae
Authors: Koutsouridou I , Salvadori S , Skúladóttir Á , Rossi M , Vanni I , Pagnini G
Published: July 2023

The nature of the first Pop III stars is still a mystery and the energy distribution of the first supernovae is completely unexplored. For the first time we account simultaneously for the unknown initial mass function (IMF), stellar mixing, and energy distribution function (EDF) of Pop III stars in the context of a cosmological model for the formation of a MW-analogue. Our data-calibrated semi-analytic model is based on a N-body simulation and follows the formation and evolution of both Pop III and Pop II/I stars in their proper time-scales. We discover degeneracies between the adopted Pop III unknowns, in the predicted metallicity and carbonicity distribution functions and the fraction of C-enhanced stars. None the less, we are able to provide the first available constraints on the EDF, $dN/dE_\star \propto E_{\star }^{-\alpha _e}$ with 1 ≤ αe ≤ 2.5. In addition, the characteristic mass of the Pop III IMF should be mch < 100 M⊙, assuming a mass range consistent with hydrodynamical simulations (0.1–1000 M⊙). Independent of the assumed Pop III properties, we find that all $\rm [C/Fe]\gt +0.7$ stars (with $\rm [Fe/H]\lt -2.8$) have been enriched by Pop III supernovae at a $\gt 20~{{\ \rm per\ cent}}$ level, and all $\rm [C/Fe]\gt +2$ stars at a $\gt 95~{{\ \rm per\ cent}}$ level. All very metal-poor stars with $\rm [C/Fe]\lt 0$ are predicted to be predominantly enriched by Pop III hypernovae and/or pair instability supernovae. To better constrain the primordial EDF, it is absolutely crucial to have a complete and accurate determination of the metallicity distribution function, and the properties of C-enhanced metal-poor stars (frequency and [C/Fe]) in the Galactic halo.
The HDAC6-RNF168 axis regulates H2A/H2A.X ubiquitination to enable double-strand break repair
Authors: Qiu Lingyu , Xu Wenchao , Lu Xiaopeng , Chen Feng , Chen Yongcan , Tian Yuan , Zhu Qian , Liu Xiangyu , Wang Yongqing , Pei Xin-Hai , Xu Xingzhi , Zhang Jun , Zhu Wei-Guo
Published: July 2023

Histone deacetylase 6 (HDAC6) mediates DNA damage signaling by regulating the mismatch repair and nucleotide excision repair pathways. Whether HDAC6 also mediates DNA double-strand break (DSB) repair is unclear. Here, we report that HDAC6 negatively regulates DSB repair in an enzyme activity-independent manner. In unstressed cells, HDAC6 interacts with H2A/H2A.X to prevent its interaction with the E3 ligase RNF168. Upon sensing DSBs, RNF168 rapidly ubiquitinates HDAC6 at lysine 116, leading to HDAC6 proteasomal degradation and a restored interaction between RNF168 and H2A/H2A.X. H2A/H2A.X is ubiquitinated by RNF168, precipitating the recruitment of DSB repair factors (including 53BP1 and BRCA1) to chromatin and subsequent DNA repair. These findings reveal novel regulatory machinery based on an HDAC6–RNF168 axis that regulates the H2A/H2A.X ubiquitination status. Interfering with this axis might be leveraged to disrupt a key mechanism of cancer cell resistance to genotoxic damage and form a potential therapeutic strategy for cancer.
The Portrayal of Premium Cigar Selling Propositions in Lifestyle Magazines: A Content Analysis
Authors: Sterling Kymberle Landrum , Franco Nicholas , Lee Eugenia , Tang Charis , Geller Amy , Mead Aimee , Anderson Maggie , Kong Grace
Published: July 2023

Introduction

Although lifestyle magazines are an important marketing tool for premium cigars, little is known about their recent portrayal of the products. We expand on research conducted for the National Academies of Sciences, Engineering, and Medicine’s Committee on Patterns of Use and Health Effects of “Premium Cigars” and Priority Research.

Aims and Methods

A content analysis of magazine covers, articles, and advertisements published in 2021 from Cigar Aficionado and Cigar Snob (five issues each) and Cigar Journal (three issues) assessed magazine themes and mentions of lower harm. Magazine covers (n = 14), advertisements (n = 105), and every fifth article (n = 45) were coded.

Results

In total, 92% of the magazine covers, 72.4% of advertisements, and 62.2% of articles had premium cigar content. Celebrities (e.g. musicians and actors) appeared on 92.9% of covers. The most common themes in the advertisements and articles were “high quality.” Regarding article content, 80% portrayed the premium cigars’ quality (e.g. superior materials), and the taste of featured products (e.g. “tones,” “aromas,” and “notes”) was portrayed in 42.4%. While no articles described their health risks, 6.7% described the positive health effects of premium cigar use (e.g. stress relief and clear cognition). Additionally, a digital search of Cigar Snob and Cigar Aficionado for terms related to lower harm (e.g. “organic,” “healthy,” “clean,” “pure,” and “natural”) found 7.7 mentions of lower-harm words per issue.

Conclusions

Our findings indicate that lifestyle magazines are an important marketing strategy that promotes and normalizes premium cigar use as a high-quality product that can have positive health effects for users.

Implications

Our manuscript characterized the premium cigar companies’ use of selling propositions, including promoting the products’ features, safety, taste, and flavors, as a part of their advertising promotion practices. Premium cigar companies used digital and print lifestyle magazines as marketing tools to promote and normalize the use of their products by emphasizing their high quality and positive health benefits (e.g. reducing stress). Premium cigars were promoted as a symbol of power and success, featured in advertisements of upscale social events (e.g. exclusive trade shows, social clubs, and lounges), and often juxtaposed with expensive alcohol, food, and other luxurious goods. Future research should assess if exposure to premium cigar content increases consumer appeal and detracts from the products’ potential adverse health outcomes.
Improving Point-of-Sale Warnings for Single Cigars: Implications for Premium Cigars
Authors: Kowitt Sarah D , Clark Sonia A , Jarman Kristen L , Cornacchione Ross Jennifer , Ranney Leah M , Sheeran Paschal , Thrasher James F , Enyioha Chineme , Goldstein Adam O
Published: July 2023

Introduction

For cigars sold individually without packaging, including many premium cigars, the US Food and Drug Administration (FDA) proposed that retailers display six warning statements on a sign at the point-of-sale (POS).

Aims and Methods

To examine the potential effectiveness of cigar warning signs, we conducted a between-subjects online experiment. Participants were 809 U.S. adults who reported using cigars (78% ever large cigar use, 49% past 30-day large cigar use) recruited from a probability-based panel. Participants viewed an image of a cigar store countertop with randomization to one of four conditions: (1) no warning sign, (2) a sign with six FDA proposed text-only warnings, (3) a sign with six novel text-only warnings, or (4) a sign with six novel text + image warnings. We used analysis of variance (ANOVA) models and post hoc Tukey tests to examine the results.

Results

The FDA-proposed text-only warning sign was perceived as less effective in discouraging participants from smoking cigars (M: 3.26, SD: 1.39; scale range: 1–5, where five indicates higher discouragement) compared with the novel text-only warning sign (M = 3.38, SD = 1.40) and the novel text + image warning sign (M = 3.65, SD = 1.34). The novel text + image warning sign increased discouragement from smoking cigars versus the FDA-proposed text-only warning sign (p = .02) and decreased the perceived satisfaction of smoking cigars versus no warning sign (p = .04). In a sensitivity analysis, the novel text + image warning sign decreased the perceived satisfaction of smoking cigars (p = .01), decreased cigar purchase intentions (p = .03), decreased the urge to smoke (p = .03), and increased discouragement from smoking cigars (p = .006) compared with all other study conditions.

Conclusions

Results provide new evidence that policymakers, such as the FDA, could use when proposing POS warning signs for cigars.

Implications

The US FDA proposed that retailers display a warning sign at the POS for cigars sold individually without packaging. We conducted an online experiment concerning the potential effectiveness of this regulatory policy with people who use cigars recruited from a probability-based panel. Results provide the first evidence that the FDA-proposed text-only warning sign was perceived as less effective than other types of warning signs and that adding images could potentially increase the effectiveness of warning signs. These findings are particularly relevant for premium cigars, which are often sold individually in brick-and-mortar retail settings.
Altered cell wall hydroxycinnamate composition impacts leaf- and canopy-level CO2 uptake and water use in rice
Authors: Pathare Varsha S , Panahabadi Rahele , Sonawane Balasaheb V , Apalla Anthony Jude , Koteyeva Nuria , Bartley Laura E , Cousins Asaph B
Published: July 2023

Cell wall properties play a major role in determining photosynthetic carbon uptake and water use through their impact on mesophyll conductance (CO2 diffusion from substomatal cavities into photosynthetic mesophyll cells) and leaf hydraulic conductance (water movement from xylem, through leaf tissue, to stomata). Consequently, modification of cell wall (CW) properties might help improve photosynthesis and crop water use efficiency (WUE). We tested this using 2 independent transgenic rice (Oryza sativa) lines overexpressing the rice OsAT10 gene (encoding a “BAHD” CoA acyltransferase), which alters CW hydroxycinnamic acid content (more para-coumaric acid and less ferulic acid). Plants were grown under high and low water levels, and traits related to leaf anatomy, CW composition, gas exchange, hydraulics, plant biomass, and canopy-level water use were measured. Alteration of hydroxycinnamic acid content led to statistically significant decreases in mesophyll CW thickness (−14%) and increased mesophyll conductance (+120%) and photosynthesis (+22%). However, concomitant increases in stomatal conductance negated the increased photosynthesis, resulting in no change in intrinsic WUE (ratio of photosynthesis to stomatal conductance). Leaf hydraulic conductance was also unchanged; however, transgenic plants showed small but statistically significant increases in aboveground biomass (AGB) (+12.5%) and canopy-level WUE (+8.8%; ratio of AGB to water used) and performed better under low water levels than wild-type plants. Our results demonstrate that changes in CW composition, specifically hydroxycinnamic acid content, can increase mesophyll conductance and photosynthesis in C3 cereal crops such as rice. However, attempts to improve photosynthetic WUE will need to enhance mesophyll conductance and photosynthesis while maintaining or decreasing stomatal conductance.
Can inequity be transmitted? Big data show the influence of physical activity inequity on socioeconomic inequity
Authors: Li Jiannan
Published: July 2023

The cumulative health effect resulting from the disparity in physical activity engagement could be transformed into out-of-pocket health expenditure in future, which would widen the socioeconomic gap on all portions of the income spectrum. Recent study reveals the association between physical activity inequity and social inequity. However, the difficulty in accurately measuring the physical activity could deter further exploration of this issue. This correspondence use smartphone-derived big data to provide a more fine-grained depiction, which suggest that the inequity in physical activity can contribute to the social inequity several years later.
Exploring Factors Conditioning the Expression of Botryosphaeria Dieback in Grapevine for Integrated Management of the Disease
Authors: Leal Catarina , Trotel-Aziz Patricia , Gramaje David , Armengol Josep , Fontaine Florence
Published: July 2023

Species from the Botryosphaeriaceae family are the causal agents of Botryosphaeria dieback (BD), a worldwide grapevine trunk disease. Because of their lifestyle and their adaptation to a wide range of temperatures, these fungi constitute a serious threat to vineyards and viticulture, especially in the actual context of climate change. Grapevine plants from both nurseries and vineyards are very susceptible to infections by botryosphaeriaceous fungi due to several cuts and wounds made during their propagation process and their entire life cycle, respectively. When decline becomes chronic or apoplectic, it reduces the longevity of the vineyard and affects the quality of the wine, leading to huge economic losses. Given the environmental impact of fungicides, and their short period of effectiveness in protecting pruning wounds, alternative strategies are being developed to fight BD fungal pathogens and limit their propagation. Among them, biological control has been recognized as a promising and sustainable alternative. However, there is still no effective strategy for combating this complex disease, conditioned by both fungal life traits and host tolerance traits, in relationships with the whole microbiome/microbiota. To provide sound guidance for an effective and sustainable integrated management of BD, by combining the limitation of infection risk, tolerant grapevine cultivars, and biological control, this review explores some of the factors conditioning the expression of BD in grapevine. Among them, the lifestyle of BD-associated pathogens, their pathogenicity factors, the cultivar traits of tolerance or susceptibility, and the biocontrol potential of Bacillus spp. and Trichoderma spp. are discussed.
The Experiences and Perceptions of Neonatal Clinicians When Using a Responsive Bassinet
Authors: Gellasch Patricia , Johnson Sandy , Walsh Tracy A.
Published: July 2023

Background:

Innovative technologies, such as the SNOO Smart Sleeper responsive bassinet (SNOO), may offer support to neonatal clinicians in their work environment.

Purpose:

The objectives of this study were to describe the experiences of clinicians when using the SNOO in their clinical settings, including their perceptions of the SNOO on the quality of infant care and their work environment.

Methods:

A retrospective, secondary analysis was conducted using 2021 survey data across 44 hospitals participating in the SNOO donation program. Respondents included 204 clinicians, predominantly neonatal nurses.

Results:

The SNOO was used in a variety of clinical scenarios, including with fussy, preterm, and healthy full-term infants, as well as substance-exposed infants experiencing withdrawal. The SNOO was perceived as a driver of positive infant and parent experiences, including enhanced quality of care. Respondents perceived the SNOO as providing them with support in their daily caring for newborns, reducing their stress, and helping them in lieu of hospital volunteers. Clinicians reported an average time savings of 2.2 hours per shift.

Implications for Practice and Research:

Results from this study provide evidence for future evaluation of the SNOO as a technology for hospitals to adopt to improve neonatal clinician satisfaction and retention, as well as improve the quality of patient care and parental satisfaction.
When to Combine Acetabular Osteotomy in Patients With Proximal Femoral Deformity Causing Residual Hip Dysplasia/Subluxation After Reduction of Developmental Dysplasia of the Hip
Authors: Cho Yoon Joo , Chae Ihn Seok , Song Mi Hyun , Shin Chang Ho , Chung Chin Youb , Choi In Ho , Cho Tae-Joon
Published: July 2023

Background:

After the successful reduction of developmental dysplasia of the hip, residual hip dysplasia may persist and lead to early osteoarthritis. Femoral and/or acetabular osteotomy has been used to address this problem. The purpose of this study is to determine the indication of femoral versus combined femoral-acetabular osteotomy in the management of residual hip dysplasia.

Methods:

Fifty-five patients with unilateral dislocated-type dysplasia of the hip, who had residual hip dysplasia after reduction, underwent femoral osteotomy with or without acetabular osteotomy before 8 years of age, and were followed for more than 2 years and over 8 years of age, were the subjects of this retrospective study. Twenty-eight patients underwent femoral osteotomy only at a median age of 34 months (group F), and 27 underwent combined femoral-Dega osteotomy at a median age of 49 months (group C). Seventeen patients in group F and 4 in group C had an additional osteotomy due to persistent hip dysplasia. Acetabular index (AI), lateral center-edge angle, and center-head distance difference were measured on serial radiographs. The z-value of AI (ZAI) was calculated. At the latest follow-up, patients in group F with Severin I/II who did not have an additional osteotomy were considered satisfactory, and patients with Severin III/IV or those who had an additional osteotomy were considered unsatisfactory. Preoperative variables were tested for the difference between satisfactory and unsatisfactory cases. Receiver operating characteristic analysis was performed to delineate a cutoff value of a significant parameter dividing the outcome.

Results:

AI and ZAI before index osteotomy were significant parameters predicting a satisfactory outcome in group F. Receiver operating characteristic analysis returned a cutoff value of ZAI 2.6 (Area Under the Curve=0.86, P=0.001). Eight of 12 cases (66.7%) with ZAI<2.6 in group F achieved a satisfactory outcome, whereas only 2 of 14 cases with ZAI ≥2.6 in group F did (P=0.02).

Conclusion:

ZAI 2.6 may serve as a threshold to combine acetabular osteotomy with femoral osteotomy in the management of residual hip dysplasia before 8 years of age.

Level of Evidence:

Therapeutic III
Comprehensive analysis of the clinical and prognostic significance of SFRP1 and PRKCB expression in non-small cell lung cancer: a retrospective analysis
Authors: Hu GuoQiang , Du Juan , Wang Bin , Song PengTao , Liu ShunLin
Published: July 2023

Objectives

Secreted frizzled-related protein 1 (SFRP1) and protein kinase C-B (PRKCB) contribute to cancer progression and angiogenesis. This study intended to detect SFRP1 and PRKCB expression in non-small-cell lung cancer (NSCLC) patients and analyze its association with clinicopathological features.

Methods

A total of 108 NSCLC patients who underwent surgical resection in our hospital between 2012 and 2017 were retrospectively analyzed. SFRP1 and PRKCB expression was detected using immunohistochemical staining. The relationships between SFRP1 and PRKCB expression and clinicopathological data were analyzed using the chi-square method. Kaplan–Meier analysis was used to investigate survival probability over time. The potential risk of NSCLC morbidity associated with SFRP1 and PRKCB levels was analyzed using univariate and multivariate Cox proportional risk models.

Results

SFRP1 and PRKCB expression was negative in 114 and 109 of the 180 NSCLC specimens, respectively. SFRP1 expression was significantly associated with TNM stage (P < 0.001) and tumor diameter (P < 0.001). PRKCB expression was significantly associated with the TNM stage (P < 0.001). The correlation between SFRP1 and PRKCB expression was evident (P = 0.023). SFRP1(−) or PRKCB(−) patients shows lower survival rates than SFRP1(+) or PRKCB(+) patients (P < 0.001). SFRP1(−)/PRKCB(−) patients had the worst prognosis (P < 0.001). Furthermore, the mortality of SFRP1(−) or PRKCB(−) patients was significantly higher than that of SFRP1(+) or PRKCB(+)

Conclusion

SFRP1 and PRKCB expression can be used to predict prognosis in patients with NSCLC.
Primary Cutaneous Epithelioid Mesenchymal Tumor With a Novel ATP2B4::GLI1 Gene Fusion
Authors: Rezaee Neda , Cohen Brandon , Eno Celeste , Shon Wonwoo
Published: July 2023

GLI1 gene alterations (rearrangement or amplification) have been found in several bone and soft tissue tumors including pericytic tumors, gastric plexiform fibromyxoma, gastroblastoma, and a various group of epithelioid tumors with regional recurrence or distant metastasis. In this article, we describe a case of primary cutaneous epithelioid mesenchymal tumor harboring hitherto not reported ATP2B4::GLI1 gene fusion. A 42-year-old man presented with a growing firm lesion on the left postauricular scalp. Microscopically, the shave biopsy specimen revealed a dermal-based nodular proliferation of relatively monotonous epithelioid cells with round to ovoid nuclei and pale eosinophilic cytoplasm, accompanied by prominent stromal vasculature. Significant cytologic atypia, necrosis, and mitotic activity were absent. The tumor cells were partially positive for CD34 and S-100 protein, but were negative for other markers, including SOX-10, keratins, and myogenic markers. An ATP2B4::GLI1 gene fusion was identified by next-generation sequencing. Array CGH was also performed, but it did not show relevant chromosomal copy number changes. Awareness of this rare cutaneous tumor, and thus, reporting of additional cases is necessary for further delineating its full clinicopathologic spectrum.
San Jie Tong Mai Fang Protects Against Atherosclerosis Progression by Regulating Macroautophagy through the PI3K/AKT/mTOR Signaling Pathway
Authors: Li Pengfei , Li Hongyu , Li Xiaohui , Li Shuangdi , Xu Hanying , Cui Junfeng , Cheng Guangyu , Liu Yinghui , Xu Xiaolin , Xin Yuning , Liu Aidong
Published: July 2023

Many studies have confirmed that macrophage autophagy injury negatively impacts the pathogenesis of atherosclerosis (AS). Meanwhile, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway affects AS progression by regulating macrophage autophagy. We previously reported that the herbal formula San Jie Tong Mai Fang (SJTMF) elicits lipid regulatory and anti-inflammatory properties. Hence, the current study used an ApoE−/− high-fat diet–fed mouse model to determine whether SJTMF elicits protective effects against AS progression by means of the regulation of macrophage autophagy through the PI3K/AKT/mTOR signaling pathway. Our results show that SJTMF reduced the number of atherosclerotic plaques, foam cell formation, and intimal thickness in mouse aorta. In addition, SJTMF improved blood lipid metabolism and inflammatory levels in mice. We also observed that SJTMF caused macrophages to be polarized toward the M2 phenotype through the inhibition of the PI3K/AKT/mTOR signaling pathway. In addition, the abundances of LC3-II/I and beclin1 proteins—key autophagy molecules—were increased, whereas that of p62 was decreased, resulting in the promotion of macrophage autophagy. Taken together, these findings indicate that SJTMF may regulate the polarization of macrophages by inhibiting the PI3K/AKT/mTOR signaling pathway, thereby reducing atherosclerotic plaque damage in ApoE−/− mice, thereby promoting macrophage autophagy and eliciting a significant antiarteriosclerosis effect. Hence, SJTMF may represent a promising new candidate drug for the treatment of AS.
Long-term Cardiovascular Adverse Events Induced by Fluoroquinolones: A Retrospective Case–control Study
Authors: Algaidi Shaima H. , Alghamdi Doaa I. , Algheffari Shimaa G. , Alzahrani Renad A. , Thabit Abrar K. , Hafiz Awatif M.
Published: July 2023

A correlation is already established between fluoroquinolones (FQs) use and cardiovascular events (CVEs), such as QT prolongation; however, serious events such as aortic aneurysm and valve regurgitation have also been reported with FQs. Several unstudied factors could contribute to the development of different CVEs that were not previously evaluated with FQ therapy. Therefore, we aimed to assess the incidence of different serious CVEs after completion of FQ therapy and potential associating factors. This was a retrospective case–control study of inpatients who received ciprofloxacin, levofloxacin, or moxifloxacin for ≥3 days. Patients' echocardiograms were evaluated for the development of aortic or valvular disease or worsening of an existing condition after completion of therapy. Of 373 included patients, 83 developed new valvular disease or worsening of an existing disease, where tricuspid valve regurgitation was the most common CVE (50/83; 60.2%), followed by mitral valve diseases (48/83; 57.8%). Aortic valve regurgitation occurred more commonly with moxifloxacin compared with ciprofloxacin and levofloxacin (17.8% vs. 6.7% and 10.7%, respectively; P = 0.01). Median time to CVE detection ranged 93–166 days for all FQs. The receipt of moxifloxacin and elevated baseline QT interval were associated with an increased CVEs risk (adjusted odds ratio 3.26; 95% confidence interval, 1.31–8.11 and adjusted odds ratio 1.02; 95% confidence interval, 1.00–1.04, respectively). Other factors did not show such association. The lack of association of different factors with the occurrence of CVEs indicates that all patients receiving FQ therapy, especially moxifloxacin, should be monitored during the first-year after therapy. Alternatively, other antibiotics with a better safety profile may be considered.
A pilot feasibility study of an ultrasound-based tool to assess muscle mass in children with liver disease
Authors: Shpoliansky Michael , Chavhan Govind B. , Zhou Alex , Ng Vicky L. , Kamath Binita M.
Published: July 2023

Background:

Sarcopenia is associated with adverse outcomes following liver transplantation, and at-risk children must be identified and prehabilitated. The gold standard for assessing sarcopenia in end-stage liver disease (ESLD) is CT assessment of the total Psoas Muscle Area (tPMA). However, radiation exposure and sedation requirements make this approach impractical for children. The bilateral anterior thigh thickness (BATT) is the cumulative measurement of the rectus femoris and vastus intermedius muscles by ultrasound and has been used to identify sarcopenia in adults. There are no studies assessing muscle mass in children using ultrasound. We hypothesized that measuring BATT with ultrasound in children with ESLD is feasible and is associated with sarcopenia.

Methods:

A prospective pilot feasibility study of patients with ESLD on the liver transplantation waitlist and age-matched healthy controls. BATT was measured by a single operator using ultrasound. tPMA indices were determined by CT imaging, along with clinical and anthropometric data.

Results:

Thirty children were studied between September 2021 and December 2022, 15 listed patients aged 4–30 months, and 15 controls aged 4–32 months. No major technical challenges or complications were encountered while performing the ultrasounds. Median BATTs of 30.8 mm (interquartile range: 27.9–32.8 mm) versus 32.7 mm (interquartile range: 31.8–36.9 mm) were demonstrated in the ESLD and control groups, respectively, and p = 0.01. A positive correlation (R = 0.603) was demonstrated between BATT and tPMA at the L4-5 level among patients with ESLD. No correlation was observed between BATT and anthropometrics.

Conclusions:

This study yields novel data on the feasibility of ultrasound to measure mid-thigh thickness in children with ESLD and suggests a correlation between BATT and tPMA, the gold standard for diagnosing sarcopenia. It sets the stage for ultrasound as a simple, noninvasive, and easily repeatable tool for assessing sarcopenia in children.
Myeloid-specific ablation of Basp1 ameliorates diet-induced NASH in mice by attenuating pro-inflammatory signaling
Authors: Meng Ziyi , Zhou Linkang , Hong Sungki , Qiu Xiaoxue , Chen Zhimin , Liu Tongyu , Inoki Ken , Lin Jiandie D.
Published: July 2023

Background and Aims:

NASH represents a severe stage of fatty liver disease characterized by hepatocyte injury, inflammation, and liver fibrosis. Myeloid-derived innate immune cells, such as macrophages and dendritic cells, play an important role in host defense and disease pathogenesis. Despite this, the nature of transcriptomic reprogramming of myeloid cells in NASH liver and its contribution to disease progression remain incompletely defined.

Approach and Results:

In this study, we performed bulk and single-cell RNA sequencing (sc-RNA seq) analysis to delineate the landscape of macrophage and dendritic cell transcriptomes in healthy and NASH livers. Our analysis uncovered cell type-specific patterns of transcriptomic reprogramming on diet-induced NASH. We identified brain-abundant membrane-attached signal protein 1 (Basp1) as a myeloid-enriched gene that is markedly induced in mouse and human NASH liver. Myeloid-specific inactivation of Basp1 attenuates the severity of diet-induced NASH pathologies, as shown by reduced hepatocyte injury and liver fibrosis in mice. Mechanistically, cultured macrophages lacking Basp1 exhibited a diminished response to pro-inflammatory stimuli, impaired NLRP3 inflammasome activation, and reduced cytokine secretion.

Conclusions:

Together, these findings uncover Basp1 as a critical regulator of myeloid inflammatory signaling that underlies NASH pathogenesis.
Serum identification of at-risk MASH: The metabolomics-advanced steatohepatitis fibrosis score (MASEF)
Authors: Noureddin Mazen , Truong Emily , Mayo Rebeca , Martínez-Arranz Ibon , Mincholé Itziar , Banales Jesus M. , Arrese Marco , Cusi Kenneth , Arias-Loste María Teresa , Bruha Radan , Romero-Gómez Manuel , Iruzubieta Paula , Aller Rocio , Ampuero Javier , Calleja José Luis , Ibañez-Samaniego Luis , Aspichueta Patricia , Martín-Duce Antonio , Kushner Tatyana , Ortiz Pablo , Harrison Stephen A. , Anstee Quentin M. , Crespo Javier , Mato José M. , Sanyal Arun J.
Published: July 2023

Background:

Early identification of those with NAFLD activity score ≥ 4 and significant fibrosis (≥F2) or at-risk metabolic dysfunction-associated steatohepatitis (MASH) is a priority as these patients are at increased risk for disease progression and may benefit from therapies. We developed and validated a highly specific metabolomics-driven score to identify at-risk MASH.

Methods:

We included derivation (n = 790) and validation (n = 565) cohorts from international tertiary centers. Patients underwent laboratory assessment and liver biopsy for metabolic dysfunction-associated steatotic liver disease. Based on 12 lipids, body mass index, aspartate aminotransferase, and alanine aminotransferase, the MASEF score was developed to identify at-risk MASH and compared to the FibroScan-AST (FAST) score. We further compared the performance of a FIB-4 + MASEF algorithm to that of FIB-4 + liver stiffness measurements (LSM) by vibration-controlled transient elastography (VCTE).

Results:

The diagnostic performance of the MASEF score showed an area under the receiver-operating characteristic curve, sensitivity, specificity, and positive and negative predictive values of 0.76 (95% CI 0.72–0.79), 0.69, 0.74, 0.53, and 0.85 in the derivation cohort, and 0.79 (95% CI 0.75–0.83), 0.78, 0.65, 0.48, and 0.88 in the validation cohort, while FibroScan-AST performance in the validation cohort was 0.74 (95% CI 0.68–0.79;p= 0.064), 0.58, 0.79, 0.67, and 0.73, respectively. FIB-4+MASEF showed similar overall performance compared with FIB-4 + LSM by VCTE (p= 0.69) to identify at-risk MASH.

Conclusion:

MASEF is a promising diagnostic tool for the assessment of at-risk MASH. It could be used alternatively to LSM by VCTE in the algorithm that is currently recommended by several guidance publications.
PTPN9 dephosphorylates FGFR2pY656/657 through interaction with ACAP1 and ameliorates pemigatinib effect in cholangiocarcinoma
Authors: Zhao Liming , Liu Jialiang , Li Kangshuai , Zhang Chao , Chen Tianli , Liu Zengli , Tang Yongchang , Hu Xiaoqiang , Shi Anda , Shu Lizhuang , Huang Shaohui , Lian Shuo , Zhang Minghui , Li Hui , Sun Jinpeng , Yu Xiao , Zhang Zhongyin , Zhang Zongli , Xu Yunfei
Published: July 2023

Abstract and Aim:

Cholangiocarcinoma (CCA) is a highly aggressive and lethal cancer that originates from the biliary epithelium. Systemic treatment options for CCA are currently limited, and the first targeted drug of CCA, pemigatinib, emerged in 2020 for CCA treatment by inhibiting FGFR2 phosphorylation. However, the regulatory mechanism of FGFR2 phosphorylation is not fully elucidated.

Approach and Results:

Here we screened the FGFR2-interacting proteins and showed that protein tyrosine phosphatase (PTP) N9 interacts with FGFR2 and negatively regulates FGFR2pY656/657. Using phosphatase activity assays and modeling the FGFR2-PTPN9 complex structure, we identified FGFR2pY656/657 as a substrate of PTPN9, and found that sec. 14p domain of PTPN9 interacts with FGFR2 through ACAP1 mediation. Coexpression of PTPN9 and ACAP1 indicates a favorable prognosis for CCA. In addition, we identified key amino acids and motifs involved in the sec. 14p-APCP1-FGFR2 interaction, including the “YRETRRKE” motif of sec. 14p, Y471 of PTPN9, as well as the PH and Arf-GAP domain of ACAP1. Moreover, we discovered that the FGFR2I654V substitution can decrease PTPN9-FGFR2 interaction and thereby reduce the effectiveness of pemigatinib treatment. Using a series of in vitro and in vivo experiments including patient-derived xenografts (PDX), we showed that PTPN9 synergistically enhances pemigatinib effectiveness and suppresses CCA proliferation, migration, and invasion by inhibiting FGFR2pY656/657.

Conclusions:

Our study identifies PTPN9 as a negative regulator of FGFR2 phosphorylation and a synergistic factor for pemigatinib treatment. The molecular mechanism, oncogenic function, and clinical significance of the PTPN9-ACAP1-FGFR2 complex are revealed, providing more evidence for CCA precision treatment.
Modified Basket Suture for a Floppy or Irregular Iris in Endothelial Keratoplasty
Authors: Ishikawa Sho , Sasaki Takanori , Maruyama Takahumi , Shinoda Kei
Published: July 2023

Performing endothelial keratoplasty in an eye with a damaged or irregular iris can result in uneven air filling, air escape behind the pupil, anterior iris curvature, a shallow anterior chamber, an uneven anterior chamber depth, difficulty inserting and opening the graft, and iris trauma. We herein present a modified basket suture technique to prevent these iris complications. Before insertion of the corneal donor graft, a double-armed 9-0 polypropylene suture on a curved needle is inserted from 4 equidistant points at the corneal limbus to create a box configuration directly anterior to the iris. These sutures prevent the iris from moving toward the cornea and the anterior chamber from becoming shallow when air replacement is performed. The suture also reduces intraoperative or postoperative iris-related problems because the air filling is more uniform and less prone to migration.
Poor Sleep Quality and Working From Home Influence the Prevalence of Leisure Time Physical Inactivity During the COVID-19 Pandemic
Authors: Moura Samara Silva , Menezes Júnior Luiz Antônio Alves , Carraro Júlia Cristina Cardoso , Machado-Coelho George Luiz Lins , Meireles Adriana Lúcia
Published: July 2023

Objective

The aim of the study is to explore possible associations according to quality of sleep and work from home (WFH) with physical inactivity (PI) during the COVID-19 pandemic.

Methods

This is a cross-sectional study in two Brazilian cities (>18 years), by probability sampling. Leisure-time physical activity was self-reported and classified according to guidelines. Sleep was by applying the Pittsburgh Sleep Quality Index. Work from home was classified as: total WFH or no WFH.

Results

A total of 1750 adults were analyzed, 69.1% were physically inactive, 51.9% had poor sleep quality, and 79.8% were not in WFH. PI was associated with poor sleep quality and non-WFH. Compared with those who reported WFH and good sleep quality, those who reported non-WFH and poor sleep quality had 4 times the prevalence of PI.

Conclusions

Poor sleep quality, and not WFH, is associated with leisure PI. These factors combined increase the probability of PI.
Effects of an Internet Delivered Behavioral Activation Program on Improving Work Engagement Among Japanese Workers
Authors: Dohi Yuri , Imamura Kotaro , Sasaki Natsu , Komase Yu , Sakuraya Asuka , Nakamura Yuri , Maejima Megumi , Aoyama Mitsuo , Kawakami Norito , Miyamoto Yuki
Published: July 2023

Objective

The aim of the study is to examine the effect of a newly developed Internet-delivered behavioral activation (iBA) program on work engagement and well-being among Japanese workers with elevated psychological distress.

Methods

Participants were recruited via an Internet survey company (N = 3299). The eligibility criteria were as follows: (1) Japanese employees aged 20 to 59 years, (2) having psychological distress, and (3) not self-employed. This iBA program was a 3-week web-based training course using behavioral activation techniques. Work engagement, psychological distress, and eudemonic well-being at work were measured at baseline and postintervention period. A paired sample t test was conducted to assess the intervention effect.

Results

Of the 568 eligible participants, 120 were randomly selected. A total of 108 participants completed the baseline survey and received the iBA program. Eighty respondents completed the postintervention survey and were included in analyses. The iBA program did not show a significant intervention effect on work engagement (P = 0.22, Cohen d = 0.14), while psychological distress (P < 0.01, d = −0.40) and role-oriented future prospects (P = 0.02, Cohen d = 0.27) were significantly improved.

Conclusions

The effect of the iBA program on work engagement may be limited.
Perceived Workplace Health Support and Severe Psychological Distress Among Japanese Workers
Authors: Ikegami Kazunori , Ando Hajime , Kurogi Kazushirou , Ogami Akira
Published: July 2023

Objective

This study aimed to assess the extent to which the intensity of perceived workplace health support (PWHS) affected the incidence of psychological distress.

Methods

At the baseline, data from 4540 eligible participants throughout Japan were obtained using an Internet survey. Among them, 2362 participants who could be followed up 1 year after the initial study were included in the analysis. The intensity of PWHS was determined using an original questionnaire. Psychological distress was assessed using the Kessler Psychological Distress Scale.

Results

Participants with high PWHS were less likely to experience severe psychological distress than those with low PWHS even after adjusting for confounding factors including work-related factors. The incidence of severe psychological distress decreased as the intensity of PWHS increased.

Conclusions

Enhanced PWHS reduced psychological distress and positively affected workers’ mental health.
Application of ChatGPT in Routine Diagnostic Pathology: Promises, Pitfalls, and Potential Future Directions
Authors: Schukow Casey , Smith Steven Christopher , Landgrebe Eric , Parasuraman Surya , Folaranmi Olaleke Oluwasegun , Paner Gladell P. , Amin Mahul B.
Published: July 2023

Large Language Models are forms of artificial intelligence that use deep learning algorithms to decipher large amounts of text and exhibit strong capabilities like question answering and translation. Recently, an influx of Large Language Models has emerged in the medical and academic discussion, given their potential widespread application to improve patient care and provider workflow. One application that has gained notable recognition in the literature is ChatGPT, which is a natural language processing “chatbot” technology developed by the artificial intelligence development software company OpenAI. It learns from large amounts of text data to generate automated responses to inquiries in seconds. In health care and academia, chatbot systems like ChatGPT have gained much recognition recently, given their potential to become functional, reliable virtual assistants. However, much research is required to determine the accuracy, validity, and ethical concerns of the integration of ChatGPT and other chatbots into everyday practice. One such field where little information and research on the matter currently exists is pathology. Herein, we present a literature review of pertinent articles regarding the current status and understanding of ChatGPT and its potential application in routine diagnostic pathology. In this review, we address the promises, possible pitfalls, and future potential of this application. We provide examples of actual conversations conducted with the chatbot technology that mimic hypothetical but practical diagnostic pathology scenarios that may be encountered in routine clinical practice. On the basis of this experience, we observe that ChatGPT and other chatbots already have a remarkable ability to distill and summarize, within seconds, vast amounts of publicly available data and information to assist in laying a foundation of knowledge on a specific topic. We emphasize that, at this time, any use of such knowledge at the patient care level in clinical medicine must be carefully vetted through established sources of medical information and expertise. We suggest and anticipate that with the ever-expanding knowledge base required to reliably practice personalized, precision anatomic pathology, improved technologies like future versions of ChatGPT (and other chatbots) enabled by expanded access to reliable, diverse data, might serve as a key ally to the diagnostician. Such technology has real potential to further empower the time-honored paradigm of histopathologic diagnoses based on the integrative cognitive assessment of clinical, gross, and microscopic findings and ancillary immunohistochemical and molecular studies at a time of exploding biomedical knowledge.
Bacterial sexually transmitted infections are concentrated in subpopulations of MSM using HIV PrEP: an analysis of longitudinal trajectories
Authors: Jongen Vita W. , Loeff Maarten F. Schim Van Der , Van Den Elshout Mark , Wijstma Eline , Coyer Liza , Davidovich Udi , Vries Henry J.C. De , Prins Maria , Hoornenborg Elske , Boyd Anders
Published: July 2023

Objective:

Studies have shown varying trends in incidence of sexually transmitted infections (STI) among individuals using HIV pre-exposure prophylaxis (PrEP). Characterization of individuals at increased risk for STIs may offer an opportunity for targeted STI screening.

Design:

Group-based trajectory modelling

Methods:

We screened participants from the AMPrEP demonstration project (2015–2020) for urogenital, anal, and pharyngeal chlamydia and gonorrhea, and syphilis every 3 months and when needed. We identified trajectories of STI incidence within individuals over time and determinants of belonging to a trajectory group. We calculated cumulative proportions of STIs within STI trajectory groups.

Results:

366 participants with baseline and ≥1 screening visit during follow-up were included (median follow-up time=3.7 years [IQR=3.5–3.7]). We identified three trajectories of STI incidence: (1) participants with a mean of approximately 0.1 STIs per 3-months (“low overall”, 52% of the population), (2) participants with a mean 0.4 STI per 3-months (“medium overall”, 43%), and (3) participants with high and fluctuating (between 0.3–1 STIs per 3-months) STI incidence (“high and fluctuating”, 5%). Participants in the “low overall” trajectory were significantly older, and reported less chemsex and condomless anal sex with casual partners than participants in the other trajectories. Participants in the “high and fluctuating” and “medium overall” groups accounted for respectively 23% and 64% of all STIs observed during follow-up.

Conclusions:

STI incidence was concentrated in subpopulations of PrEP users who were younger, had more chemsex and condomless anal sex. Screening frequency for STIs could be reduced for subpopulations with low risk for incident STIs.
Perfusion Computed Tomography in Rectal Carcinoma: Influence of Optimization of the Patlak Range on Calculation of Equivalent Blood Volume and Flow Extraction
Authors: Talakić Emina , Kaufmann-Bühler Ann-Katrin , Igrec Jasminka , Adelsmayr Gabriel , Janisch Michael , Döller Carmen , Geyer Edith , Lackner Karoline , Fuchsjäger Michael , Schöllnast Helmut
Published: July 2023

Purpose

The aim of the study is to assess the influence of manual adjustment of the Patlak range in computed tomography (CT) perfusion analysis of rectal carcinoma compared with default range of the perfusion software.

Methods

This study was approved by the institutional review board and informed consent was obtained. Twenty-one patients (12 male, 9 female; mean age ± SD, 59 ± 11 years) with rectal cancer were included and underwent perfusion CT before preoperative chemoradiotherapy. Equivalent blood volume (BV) and flow-extraction (FE) were calculated using the Patlak plot model. Two perfusion sets were calculated per patient, a perfusion set using the default setting as provided by the software (dBV, dFE) and an optimized perfusion set after manual adaption of the Patlak range (aBV, aFE), which was limited to the intravascular space clearance of contrast to the extravascular space. Perfusion values calculated with both methods were compared for significance in differences using the Wilcoxon test. A P value of 0.05 or less was defined as statistically significant.

Results

Adjustment of the Patlak range statistically significantly influenced BV and FE calculation. Median dBV was 23.2 mL/100 mL (interquartile range [IQR], 12.1 mL/100 mL), whereas median aBV was 20.3 mL/100 mL (IQR, 10.9 mL/100 mL). The difference in BV was statistically significant (P = 0.021). Median dFE was 8.3 mL/min/100 mL (IQR, 4.7 mL/min/100 mL), whereas median aFE was 15.4 mL/min/100 mL (IQR, 5.8 mL/min/100 mL). The difference in FE was statistically significant (P < 0.001).

Conclusions

Our findings indicate that in perfusion CT of rectal carcinoma, adjustment of the Patlak range may significantly influence BV and FE compared with default setting of the software. This may contribute to standardization in the use of this technique for functional imaging of rectal cancer.