bluuebunny/crossref_metadata_2025 huggingface dataset:
Missed Opportunities in Geriatric Oncology Research
Authors: Lichtman Stuart M
Published: March 2023

The field of geriatric oncology has made significant progress in recent decades, but there are still missed opportunities in important areas of research. One issue is the underrepresentation of older patients, especially those aged 75 years and older, in clinical trials. This has resulted in a lack of high-quality data for the care of this population, and the American Society of Clinical Oncology has called for an increase in the evidence base for older patients with cancer. The second missed opportunity is the chance to gather important knowledge from older patients participating in clinical trials, such as medications, social support, insurance, and financial information. These data can be easily collected and incorporated into the trial design to enhance the information available to researchers and clinicians. The third missed opportunity is the chance to robustly analyze and report clinical trial data for the benefit of geriatric oncology research. Many trials only report a median age and range, which is a disservice to both the participants and the patients who will be treated based on the study results. To advance geriatric oncology research, the necessary data need to be collected, analyzed, and reported through appropriate representation of older patients, collection of essential information, and thorough analysis and communication of results. Clinical trial design needs to include geriatric baseline parameters, and Cancer Therapy Evaluation Program (CTEP) has modified its template to include these parameters.
Spectral study of the Galactic ridge X-ray emission with Suzaku: Comparison of the spectral shape with point sources
Authors: Yamamoto Kumiko , Yamauchi Shigeo , Nobukawa Masayoshi , Nobukawa Kumiko K , Uchiyama Hideki
Published: March 2023

The Galactic ridge X-ray emission (GRXE) is unresolved X-ray emission located on the Galactic plane, and whether the GRXE comes from truly diffuse plasma or unresolved point sources is still debatable. We present results of spectral analysis of the GRXE with Suzaku. In order to examine the point source origin, we fitted the GRXE spectra in the 1.2–10 keV energy band with a point source model, which is a mixture of active binary stars (ABs) and non-magnetic cataclysmic variables (non-mCVs), and found that the model cannot represent the GRXE spectral shape as long as the standard metal abundances of these species are assumed. In particular, the standard abundance model cannot account for the observed intensities of Si, S, and Ar lines as well as the previously reported Fe line. Assuming spatial densities in the solar neighborhood, integration of the ABs and non-mCVs accounts for only 30% of the observed GRXE flux. Other species of the point sources or diffuse emission with stronger Si, S, Ar, and Fe emission lines shall explain the rest.
Willingness toward psychosocial support during cancer treatment: a critical yet challenging construct in psychosocial care
Authors: Parmet Tamar , Yusufov Miryam , Braun Ilana M , Pirl William F , Matlock Daniel D , Sannes Timothy S
Published: March 2023

Psychosocial distress screening, mandated by the American College Surgeons’ Commission on Cancer, continues to be implemented across cancer centers nationwide. Although measuring distress is critical to identifying patients who may benefit from additional support, several studies suggest that distress screening may not actually increase patients’ utilization of psychosocial services. While various investigators have identified barriers that may impede effective implementation of distress screening, we posit that patients’ intrinsic motivation, which we term patients’ willingness, may be the biggest predictor for whether cancer patients choose to engage with psychosocial services. In this commentary, we define patient willingness towards psychosocial services as a novel construct, distinct from the intention toward a certain behavior described across pre-existing models of health behavior change. Further, we offer a critical perspective of models of intervention design that focus on acceptability and feasibility as preliminary outcomes thought to encompass the willingness construct described herein. Finally, we summarize several health service models that successfully integrate psychosocial services alongside routine oncology care. Overall, we present an innovative model that acknowledges barriers and facilitators and underscores the critical role of willingness in health behavior change. Consideration of patients’ willingness toward psychosocial care will move the field of psychosocial oncology forward in clinical practice, policy initiatives, and study design.
Implementation planning for equitable tobacco treatment services: a mixed methods assessment of contextual facilitators and barriers in a large comprehensive cancer center
Authors: Tsui Jennifer , Sloan Kylie , Sheth Rajiv , Ewusi Boisvert Esthelle , Nieva Jorge , Kim Anthony W , Pang Raina D , Sussman Steve , Kirkpatrick Matthew
Published: March 2023

Tobacco use among cancer patients is associated with an increased mortality and poorer outcomes, yet two-thirds of patients continue using following diagnosis, with disproportionately higher use among racial/ethnic minority and low socioeconomic status patients. Tobacco treatment services that are effectively tailored and adapted to population characteristics and multilevel context specific to settings serving diverse patients are needed to improve tobacco cessation among cancer patients. We examined tobacco use screening and implementation needs for tobacco treatment services to inform equitable and accessible delivery within a large comprehensive cancer center in the greater Los Angeles region.

We conducted a multi-modal, mixed methods assessment using electronic medical records (EMR), and clinic stakeholder surveys and interviews (guided by the Consolidated Framework for Implementation Research).

Approximately 45% of patients (n = 11,827 of 26,030 total) had missing tobacco use history in their EMR. Several demographic characteristics (gender, age, race/ethnicity, insurance) were associated with greater missing data prevalence. In surveys (n = 32), clinic stakeholders endorsed tobacco screening and cessation services, but indicated necessary improvements for screening/referral procedures. During interviews (n = 13), providers/staff reported tobacco screening was important, but level of priority differed as well as how often and who should screen. Several barriers were noted, including patients’ language/cultural barriers, limited time during visits, lack of smoking cessation training, and insurance coverage.

While stakeholders indicated high interest in tobacco use assessment and cessation services, EMR and interview data revealed opportunities to improve tobacco use screening across patient groups. Implementing sustainable system-level tobacco cessation programs at institutions requires leadership support, staff training, on routine screening, and intervention and referral strategies that meet patients’ linguistic/cultural needs.
Equity and behavioral digital health interventions: Strategies to improve benefit and reach
Authors: Miller Sarah J , Sly Jamilia R , Alcaraz Kassandra I , Ashing Kimlin , Christy Shannon M , Gonzalez Brian , Lu Qian , Newton Robert L , Redmond Michelle , Shen Megan , Thomas-Purcell Kamilah , Yi Jean , Veinot Tiffany , Meade Cathy D
Published: March 2023

Background

Behavioral digital health interventions (e.g., mobile apps, websites, wearables) have been applied widely to improve health outcomes. However, many groups (e.g., people with low income levels, people who are geographically isolated, older adults) may face obstacles to technology access and use. In addition, research has found that biases and stereotypes can be embedded within digital health interventions. As such, behavioral digital health interventions that intend to improve overall population health may unintentionally widen health-related inequities.

Purpose

This commentary offers guidance and strategies to mitigate these risks when using technology as a means for delivering a behavioral health intervention.

Methods

A collaborative working group from Society of Behavioral Medicine’s Health Equity Special Interest Group developed a framework to center equity in the development, testing and dissemination of behavioral digital health interventions.

Results

We introduce Partner, Identify, Demonstrate, Access, Report (PIDAR), a 5-point framework to avoid the creation, perpetuation, and/or widening of health inequities in behavioral digital health work.

Conclusions

It is critically important to prioritize equity when conducting digital health research. The PIDAR framework can serve as a guide for behavioral scientists, clinicians and developers.
Air sac attachments or tendon scars: the distinction between soft tissue traces in archosaur bone
Authors: Aureliano Tito , Ghilardi Aline M , Fernandes Marcelo A , Ricardi-Branco Fresia S
Published: March 2023

It can be arduous to discriminate between lamellar bone fibres, Sharpey’s fibres (tendon insertions) and the pneumosteum (air sac diverticula interaction with the bone) during histological observations. We analysed thin sections of several avemetatarsalians from the Cretaceous of Brazil and used characters from optical mineralogy to differentiate these biomineralized tissue types, resulting in a solid criterion for histological comparison. The observation scale is one of the best guides to differentiate the tissues. Lamellar bone fibres are only perceptible at very high magnifications (100×) whereas Sharpey’s fibres are detectable at low magnification (5×). Pneumosteal bone fibres are discernible at 40–50×. Hence, fibre length is longer in Sharpey’s fibres than in the pneumosteum. High optical relief is a good proxy to detect connective tissue insertion scars (Sharpey’s fibres). Finally, texture is an excellent proxy to identify pneumosteal bone. The asbestiform aspect of this structure is so far unique among several bone tissue types.
What Can Be Learned by a Synoptic Review of Plant Disease Epidemics and Outbreaks Published in 2021?
Authors: Jeger Michael J. , Fielder Hannah , Beale Tim , Szyniszewska Anna M. , Parnell Stephen , Cunniffe Nik J.
Published: March 2023

A synoptic review of plant disease epidemics and outbreaks was made using two complementary approaches. The first approach involved reviewing scientific literature published in 2021, in which quantitative data related to new plant disease epidemics or outbreaks were obtained via surveys or similar methodologies. The second approach involved retrieving new records added in 2021 to the CABI Distribution Database, which contains over a million global geographic records of organisms from over 50,000 species. The literature review retrieved 186 articles, describing studies in 62 categories (pathogen species/species complexes) across more than 40 host species on six continents. Pathogen species with more than five articles were Bursaphelenchus xylophilus, ‘ Candidatus Liberibacter asiaticus’, cassava mosaic viruses, citrus tristeza virus, Erwinia amylovora, Fusarium spp. complexes, F. oxysporum f. sp. cubense, Magnaporthe oryzae, maize lethal necrosis co-infecting viruses , Meloidogyne spp. complexes, Pseudomonas syringae pvs., Puccinia striiformis f. sp. tritici, Xylella fastidiosa, and Zymoseptoria tritici. Automated searches of the CABI Distribution Database identified 617 distribution records new in 2021 of 283 plant pathogens. A further manual review of these records confirmed 15 pathogens reported in new locations: apple hammerhead viroid, apple rubbery wood viruses, Aphelenchoides besseyi, Biscogniauxia mediterranea, ‘ Ca. Liberibacter asiaticus’, citrus tristeza virus, Colletotrichum siamense, cucurbit chlorotic yellows virus, Erwinia rhapontici, Erysiphe corylacearum, F. oxysporum f. sp. cubense Tropical race 4, Globodera rostochiensis, Nothophoma quercina, potato spindle tuber viroid, and tomato brown rugose fruit virus. Of these, four pathogens had at least 25% of all records reported in 2021. We assessed two of these pathogens—tomato brown rugose fruit virus and cucurbit chlorotic yellows virus—to be actively emerging in/spreading to new locations. Although three important pathogens—‘ Ca. Liberibacter asiaticus’, citrus tristeza virus, and F. oxysporum f. sp. cubense—were represented in the results of both our literature review and our interrogation of the CABI Distribution Database, in general, our dual approaches revealed distinct sets of plant disease outbreaks and new records, with little overlap.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license .
Virulence Profiles and Genome-Wide Association Study for Ascochyta lentis Isolates Collected from Australian Lentil-Growing Regions
Authors: Henares Bernadette M. , Blake Sara N. , Farfan-Caceres Lina , Tahghighi Hediyeh , Debler Johannes W. , Russ Michelle H. , Farquharson Elizabeth A. , Rose Jade A. , Khani Mohsen , Davidson Jennifer A. , Kamphuis Lars G. , Lee Robert C.
Published: March 2023

Ascochyta lentis, the causal organism of Ascochyta blight (AB) of lentil ( Lens culinaris), has been shown to produce an avirulence effector protein that mediates AB resistance in certain lentil cultivars. The two known forms of the effector protein were identified from a biparental mapping population between isolates that have reciprocal virulence on ‘PBA Hurricane XT’ and ‘Nipper’. The effector AlAvr1-1 was described for the PBA Hurricane XT-avirulent isolate P94-24 and AlAvr1-2 characterized in the PBA Hurricane XT-virulent isolate AlKewell. Here, we performed a genome-wide association study to identify other loci associated with AB for a differential set of lentil cultivars from a diverse panel of isolates collected in the Australian lentil-growing regions from 2013 to 2020. The chromosome 3 AlAvr1 locus was strongly associated with the PBA Hurricane XT, ‘Indianhead’, and Nipper disease responses, but one other genomic region on chromosome 11 was also associated with the Nipper disease trait. Our results corroborate earlier work that identified the AlAvr1 locus for field-collected isolates that span the period before release and after widespread adoption of PBA Hurricane XT. A multiplex PCR assay was developed to differentiate the genes AlAvr1-1 and AlAvr1-2 to predict PBA Hurricane XT avirulence and pathotype designation in the diversity panel. Increasing numbers of the PBA Hurricane XT-virulent pathotype 2 isolates across that time indicate strong selection for isolates with the AlAvr1-2 allele. Furthermore, one other region of the A. lentis genome may contribute to the pathogen–host interaction for lentil AB.
Obesogenic diet leads to luminal overproduction of the complex IV inhibitor H2S and mitochondrial dysfunction in mouse colonocytes
Authors: Guerbette Thomas , Beaumont Martin , Andriamihaja Mireille , Ciesielski Vincent , Perrin Jean‐Baptiste , Janvier Régis , Randuineau Gwénaëlle , Leroyer Patricia , Loréal Olivier , Rioux Vincent , Boudry Gaëlle , Lan Annaïg
Published: March 2023

Obesity is characterized by systemic low‐grade inflammation associated with disturbances of intestinal homeostasis and microbiota dysbiosis. Mitochondrial metabolism sustains epithelial homeostasis by providing energy to colonic epithelial cells (CEC) but can be altered by dietary modulations of the luminal environment. Our study aimed at evaluating whether the consumption of an obesogenic diet alters the mitochondrial function of CEC in mice. Mice were fed for 22 weeks with a 58% kcal fat diet (diet‐induced obesity [DIO] group) or a 10% kcal fat diet (control diet, CTRL). Colonic crypts were isolated to assess mitochondrial function while colonic content was collected to characterize microbiota and metabolites. DIO mice developed obesity, intestinal hyperpermeability, and increased endotoxemia. Analysis of isolated colonic crypt bioenergetics revealed a mitochondrial dysfunction marked by decreased basal and maximal respirations and lower respiration linked to ATP production in DIO mice. Yet, CEC gene expression of mitochondrial respiration chain complexes and mitochondrial dynamics were not altered in DIO mice. In parallel, DIO mice displayed increased colonic bile acid concentrations, associated with higher abundance of Desulfovibrionaceae. Sulfide concentration was markedly increased in the colon content of DIO mice. Hence, chronic treatment of CTRL mouse colon organoids with sodium sulfide provoked mitochondrial dysfunction similar to that observed in vivo in DIO mice while acute exposure of isolated mitochondria from CEC of CTRL mice to sodium sulfide diminished complex IV activity. Our study provides new insights into colon mitochondrial dysfunction in obesity by revealing that increased sulfide production by DIO‐induced dysbiosis impairs complex IV activity in mouse CEC.
Intraoperative Antibiotic Use in Patients With Early-onset Scoliosis: Current Practices and Trends
Authors: Faust Millis , Allahabadi Sachin , Louer Craig , Sponseller Paul , Strum Peter , Boachie-Adjei Oheneba , Oetgen Matthew ,   Pediatric Spine Study Group, Swarup Ishaan
Published: March 2023

Background:

Best Practice Guidelines (BPGs) regarding antibiotic prophylaxis in early-onset scoliosis (EOS) patients were published in September 2019. Recommendations included using intravenous cefazolin and topical vancomycin for all index procedures, plus gram-negative coverage for neuromuscular patients. Guideline adherence is unknown. This study aimed to characterize antibiotic prophylaxis at the time of index growth-friendly procedures and assess changes in practice patterns over time.

Materials and Methods:

This retrospective review of data collected through a multicenter study group included EOS patients undergoing index growth-friendly procedures between January 2018 and March 2021, excluding revisions, lengthenings, and tetherings. Demographics, clinical measurements, intraoperative antibiotics, and 90-day complications were recorded. Descriptive and univariate statistics were utilized. Antibiotic prophylaxis from April 2018 through September 2019 and October 2019 through March 2021 were compared with evaluate change after BPG publication.

Results:

A total of 562 patients undergoing growth-friendly procedures were included. The most common scoliosis types included neuromuscular (167, 29.7%), syndromic (134, 23.8%), and congenital (97, 17.3%). Most index procedures involved magnetically controlled growing rods (417, 74%) followed by vertical expandable prosthetic titanium rib or traditional growing rods (105, 19%). Most patients received cefazolin alone at index procedure (310, 55.2%) or cefazolin with an aminoglycoside (113, 20.1%). Topical antibiotics were used in 327 patients (58.2%), with most receiving vancomycin powder. There was increased use of cefazolin with an aminoglycoside after BPG publication (16% vs. 25%) (P=0.01). Surgical site infections occurred in 12 patients (2.1%) within 90 days of index procedure, 10 pre-BPGs (3%), and 2 post-BPGs (0.9%), with no significant difference in surgical site infection rate by type of antibiotic administered (P>0.05).

Conclusions:

Historical variability exists regarding antibiotic prophylaxis during index growth-friendly procedures for EOS. There continues to be variability following BPG publication; however, this study found a significant increase in antibiotic prophylaxis against gram-negative bacteria after BPG publication. Overall, greater emphasis is needed to decrease variability in practice, improve compliance with consensus guidelines, and evaluate BPG efficacy.

Level of Evidence:

Level III—retrospective.
Fluid Overload Precedes and Masks Cryptic Kidney Injury in Pediatric Acute Respiratory Distress Syndrome
Authors: Dixon Celeste G. , Thadani Sameer , Fitzgerald Julie C. , Akcan-Arikan Ayse , Yehya Nadir
Published: March 2023

OBJECTIVES:

Given the complex interrelatedness of fluid overload (FO), creatinine, acute kidney injury (AKI), and clinical outcomes, the association of AKI with poor outcomes in critically ill children may be underestimated due to definitions used. We aimed to disentangle these temporal relationships in a large cohort of children with acute respiratory distress syndrome (ARDS).

DESIGN:

Retrospective cohort study.

SETTING:

Quaternary care PICU.

PATIENTS:

Seven hundred twenty intubated children with ARDS between 2011 and 2019.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Daily fluid balance, urine output (UOP), and creatinine for days 1–7 of ARDS were retrospectively abstracted. A subset of patients had angiopoietin 2 (ANGPT2) quantified on days 1, 3, and 7. Patients were classified as AKI by Kidney Disease Improving Global Outcomes (KDIGO) stage 2/3 then grouped by timing of AKI onset (early if days 1–3 of ARDS, late if days 4–7 of ARDS, persistent if both) for comparison of PICU mortality and ventilator-free days (VFDs). A final category of “Cryptic AKI” was used to identify subjects who met KDIGO stage 2/3 criteria only when creatinine was adjusted for FO. Outcomes were compared between those who had Cryptic AKI identified by FO-adjusted creatinine versus those who had no AKI. Conventionally defined AKI occurred in 26% of patients (early 10%, late 3%, persistent 13%). AKI was associated with higher mortality and fewer VFDs, with no differences according to timing of onset. The Cryptic AKI group (6% of those labeled no AKI) had higher mortality and fewer VFDs than patients who did not meet AKI with FO-adjusted creatinine. FO, FO-adjusted creatinine, and ANGPT2 increased 1 day prior to meeting AKI criteria in the late AKI group.

CONCLUSIONS:

AKI was associated with higher mortality and fewer VFDs in pediatric ARDS, irrespective of timing. FO-adjusted creatinine captures a group of patients with Cryptic AKI with outcomes approaching those who meet AKI by traditional criteria. Increases in FO, FO-adjusted creatinine, and ANGPT2 occur prior to meeting conventional AKI criteria.
Vesicular Lymphomatoid Papulosis With DUSP22-IRF4 Rearrangement on Chromosome 6p25.3: A Case Report
Authors: Pan Po-Yang , Liao Jia-Bin , Hsieh Shu-Min , Tseng Hui-Wen
Published: March 2023

Lymphomatoid papulosis (LyP) with DUSP22-IRF4 rearrangement on chromosome 6p25.3 is a newly identified subtype of LyP. It is characterized by an older age of onset, localized skin lesions, with good prognosis, and it resembles a hybrid of LyP types B and C in histopathology. A limited number of cases have been reported so far. In this article, we reported a case of a 72-year-old man with recurrent episodes of widespread multiple discrete papular or vesicular eruptions on a region of the head, trunk, and 4 extremities for about 3 years. Histopathological examination of a vesicle revealed a subepidermal blister with abundant atypical lymphocytes in the vesicular space, band-like infiltrates in the papillary dermis, along with epidermotropism and pilosebaceous structure involvement. Fluorescence in situ hybridization analysis further demonstrated DUSP22-IRF4 rearrangement on chromosome 6p25.3. A diagnosis of vesicular LyP with this rare subtype was made according to the clinical and pathological findings.
Spitz Tumor With SQSTM1::NTRK2 Fusion: A Clinicopathological Study of 5 Cases
Authors: Mansour Boulos , Vanecek Tomas , Kastnerova Liubov , Nosek Daniel , Kazakov Dmitry V. , Donati Michele
Published: March 2023

Spitz tumors are melanocytic neoplasms characterized by specific, mutually exclusive driver molecular events, namely genomic rearrangements involving the threonine kinaseBRAFand the tyrosine kinase receptorsALK,NTRK1,NTRK2,NTRK3,MET,RET,ROS1, andMAP3K8or less commonly, mutations inHRASorMAP2K1. We hereby report 5 Spitz tumors with aSQSTM1::NTRK2fusion. All patients were woman with the ages at diagnosis ranging from 30 to 50 years. Locations included the lower extremity (n = 3), forearm, and back (one each). All the neoplasms were superficial melanocytic proliferation with a flat to dome-shaped silhouette, in which junctional spindled and polygonal dendritic melanocytes were mainly arranged as horizontal nests associated with conspicuous lentiginous involvement of the follicular epithelium. Only one case showed heavily pigmented, vertically oriented melanocytic nests resembling Reed nevus. A superficial intradermal component observed in 2 cases appeared as small nests with a back-to-back configuration. In all lesions, next-generation sequencing analysis identified aSQSTM1::NTRK2fusion. A single case studied with fluorescence in situ hybridization for copy number changes in melanoma-related genes proved negative. No further molecular alterations were detected, includingTERT-photspot mutations.
Topical Lidocaine or Lidocaine/Diltiazem Ointment Following Rubber Band Ligation of Hemorrhoids: A Prospective Three-Armed Randomized Controlled Trial
Authors: Kwok Allan M.F. , Smith Stephen R. , Zhao Jie , Carroll Rosemary , Leigh Lucy , Draganic Brian
Published: March 2023

BACKGROUND:

Rubber band ligation of hemorrhoids causes less pain than excisional hemorrhoidectomy, but many patients still experience significant post-procedure discomfort.

OBJECTIVE:

This study aims to determine if topical lidocaine, with or without diltiazem, is more effective than placebo for analgesia following hemorrhoid banding.

DESIGN:

This is a prospective, randomized, double-blinded, placebo controlled trial. Patients were randomized to 2% lidocaine, 2% lidocaine with 2% diltiazem, or placebo ointment.

SETTINGS:

This study was performed at two university public teaching hospitals and 2 private hospitals in Australia.

PATIENTS:

Consecutive patients aged ≥18 years undergoing hemorrhoid banding were selected.

INTERVENTIONS:

Topical ointments were applied post-procedure 3 times daily for 5 days.

MAIN OUTCOME MEASURES:

Visual analogue pain score, opiate analgesia usage, and patient satisfaction were the main outcome measures.

RESULTS:

Of 159 eligible patients, 99 were randomized (33 in each group). Pain scores were reduced at 1 hour for the lidocaine (OR 4.15 [1.12-15.41] p = 0.03) and lidocaine/diltiazem groups (OR 3.85 (1.05-14.11), p = 0.04) compared with placebo. Patients in the lidocaine/diltiazem group had improved satisfaction (OR 3.82 [1.28-11.44], p = 0.02) and were more likely to recommend the procedure to others (OR 9.33 [1.07-81.72] p = 0.04). Patients in the lidocaine/diltiazem group required approximately 45% less total and in-hospital analgesia compared with placebo. There was no difference in complications between any of the groups.

LIMITATIONS:

A cost/benefit analysis was not performed. Analgesic efficacy appeared to be short-term and the procedures were performed only in the hospital/non-ambulatory setting.

CONCLUSION:

Topical lidocaine improves short-term analgesia, while combination lidocaine/diltiazem is associated with both improved analgesia and patient satisfaction following hemorrhoid banding.
Parathyroid hormone receptor-1 signaling aggravates hepatic fibrosis through upregulating cAMP response element-binding protein-like 2
Authors: Hong Ting , Xiong Xuelian , Chen Yaqiong , Wang Qiuyu , Fu Xiao , Meng Qingnan , Lu Yan , Li Xiaoying
Published: March 2023

Background and Aims:

Parathyroid hormone receptor-1 (PTH1R) is a class B G protein–coupled receptor central to skeletal development, bone turnover, and calcium homeostasis. However, the role of PTH1R signaling in liver fibrosis is largely unknown. Here, the role of PTH1R signaling in the activation of HSCs and hepatic fibrosis was examined.

Approach and Results:

PTH1R was highly expressed in activated HSCs and fibrotic liver by using human liver specimens or carbon tetrachloride (CCl4)-treated or methionine and choline-deficient diet (MCD)-fed C57/BL6 mice. The mRNA level of hepatic PTH1R was positively correlated to α-smooth muscle actin in patients with liver cirrhosis. Mice with HSCs-specific PTH1R deletion were protected from CCl4, MCD, or western diet, plus low-dose CCl4-induced liver fibrosis. Conversely, parathyroid hormone (PTH) aggravated liver fibrosis in CCl4-treated mice. Mouse primary HSCs and LX2 cell lines were used for in vitro experiments. Molecular analyses by luciferase reporter assays and chromatin immunoprecipitation assays in combination with mRNA sequencing in HSCs revealed that cAMP response element-binding protein-like 2 (Crebl2), a novel regulator in HSCs treated by PTH that interacted with mothers against decapentaplegic homolog 3 (SMAD3) and increased the transcription of TGFβ in activating HSCs and collagen deposition. In agreement, HSCs-specific Crebl2 deletion ameliorated PTH-induced liver fibrosis in CCl4-treated mice.

Conclusions:

In both mouse and human models, we found that PTH1R was highly expressed in activated HSCs and fibrotic liver. PTH1R signaling regulated collagen production in the HSCs through Crebl2/SMAD3/TGFβ regulatory circuits. Blockade of PTH1R signaling in HSCs might help mitigate the development of liver fibrosis.
Efficacy of segmented axial length and artificial intelligence approaches to intraocular lens power calculation in short eyes
Authors: Kenny Peter I. , Kozhaya Karim , Truong Paulina , Weikert Mitchell P. , Wang Li , Hill Warren E. , Koch Douglas D.
Published: March 2023

Purpose:

In short eyes, to compare the predictive accuracy of newer intraocular lens (IOL) power calculation formulas using traditional and segmented axial length (AL) measurements.

Setting:

Cullen Eye Institute, Baylor College of Medicine, Houston, Texas and East Valley Ophthalmology, Mesa, Arizona.

Design:

Multi-center retrospective case series.

Methods:

Measurements from an optical biometer were collected in eyes with AL <22 mm. IOL power calculations were performed with 15 formulas using 2 AL values: (1) machine-reported traditional AL (Td-AL) and (2) segmented AL calculated with the Cooke-modified AL nomogram (CMAL). 1 AL method and 7 formulas were selected for pairwise analysis of mean absolute error (MAE) and root mean square absolute error (RMSAE).

Results:

The study comprised 278 eyes. Compared with the Td-AL, the CMAL produced hyperopic shifts without differences in RMSAE. The ZEISS AI IOL Calculator (ZEISS AI), K6, Kane, Hill-RBF, Pearl-DGS, EVO, and Barrett Universal II (Barrett) formulas with Td-AL were compared pairwise. The ZEISS AI demonstrated smaller MAE and RMSAE than the Barrett, Pearl-DGS, and Kane. K6 had a smaller RMSAE than the Barrett formula. In 73 eyes with shallow anterior chamber depth, the ZEISS AI and Kane had a smaller RMSAE than the Barrett.

Conclusions:

ZEISS AI outperformed Barrett, Pearl-DGS, and Kane. The K6 formula outperformed some formulas in selected parameters. Across all formulas, use of a segmented AL did not improve refractive predictions.
Urinary Bladder Cancer in Bladder Exstrophy and Epispadias Complex: A Swedish Register Study and a Systematic Review of the Literature
Authors: Arkani Samara , Skarin Nordenvall Anna , Renström Koskela Lotta , Reinfeldt Engberg Gisela , Nordgren Ann , Nordenskjöld Agneta
Published: March 2023

The congenital malformation bladder exstrophy and epispadias complex involves multiple organs and includes 3 subtypes: epispadias, classic bladder exstrophy, and cloacal exstrophy. The risk of urinary bladder cancer is known to be higher in individuals with classic bladder exstrophy and appears at a younger age compared with the general population.

Purpose:

The purpose of this study was to evaluate urinary bladder cancer in individuals with bladder exstrophy and epispadias complex.

Materials and Methods:

We performed 2 studies, a Swedish register-based case series reporting 12 novel cases and a systematic review summarizing published cases thus far. MEDLINE, EMBASE, Web of Science, and Google Scholar were searched in January 2022 following the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Publications reporting at least 1 case of bladder exstrophy and epispadias complex with urinary bladder cancer were eligible. Ninety-seven publications were included, reporting 165 cases.

Results:

The main result from the register study was the tumors being predominantly urothelial. Conversely, earlier published cases from the literature had a nonurothelial tumor type in 95%, whereof the majority were adenocarcinomas. Both substudies consistently indicate a young age at cancer diagnosis, with the majority being younger than 65 years.

Conclusions:

Urinary bladder cancer affects individuals with bladder exstrophy and epispadias complex at a young age. The most common tumor type in the register study is urothelial. The divergence between the 2 substudies in tumor types could reflect a slightly older age in our case series, likewise a possible publication bias.
Characteristics of Mpox Vaccine Recipients Among a Sample of Men Who Have Sex With Men With Presumed Exposure to Mpox
Authors: Abara Winston E. , Sullivan Patrick , Carpino Tom , Sanchez Travis , Atkins Kaitlyn , Delaney Kevin , Edwards O. Winslow , Hannah Marissa , Baral Stefan , Ogale Yasmin , Galloway Eboni , Lansky Amy
Published: March 2023

Mpox vaccination is recommended for persons exposed to or at risk for mpox. Approximately 25% of an online sample of men who have sex with men (MSM) with presumed mpox exposure were vaccinated (≥1 dose). Vaccination was higher among younger MSM, MSM concerned about mpox, or MSM reporting sexual risk behaviors. Incorporating mpox vaccination into routine sexual health care and increasing 2-dose vaccination uptake is essential to preventing mpox acquisition, improving MSM sexual health, and averting future mpox outbreaks.
Sexually Transmitted Infection/Human Immunodeficiency Virus, Pregnancy, and Mental Health-Related Services Provided During Visits With Sexual Assault and Abuse Diagnosis for US Medicaid Beneficiaries, 2019
Authors: Tao Guoyu , Li Jingjing , Johns Michelle , Patel Chirag G. , Workowski Kimberly
Published: March 2023

Background

Centers for Disease Control recommends that the decision to provide sexually transmitted infection (STI)/human immunodeficiency virus (HIV) testing and presumptive treatment to patients who report sexual assault and abuse (SAA) be made on an individual basis.

Methods

The 2019 Centers for Medicare & Medicaid Services national Medicaid data set was used. The SAA visits were identified by International Classification of Diseases 10th Revision Clinical Modification (O9A4 for pregnancy-related sexual abuse, T74.2 for confirmed sexual abuse, and Z04.4 for alleged rape). The initial SAA visit was defined as the patient's first SAA-related visit. Medical services were identified by International Classification of Diseases 10th Revision Clinical Modification codes, Current Procedural Terminology codes, and National Drug Code codes.

Results

Of 55,113 patients at their initial SAA visits, 86.2% were female; 63.4% aged ≥13 years; 59.2% visited emergency department (ED); all STI/HIV tests were provided in ≤20% of visits; presumptive gonorrhea and chlamydia treatment was provided in 9.7% and 3.4% of visits, respectively; pregnancy test was provided in 15.7% of visits and contraception services was provided in 9.4% of visits; and diagnosed anxiety was provided in 6.4% of visits. Patients who visited ED were less likely to have STI testing and anxiety than those visited non-ED facilities, but more likely to receive presumptive treatment for gonorrhea, testing for pregnancy, and contraceptive services. About 14.2% of patients had follow-up SAA visits within 60 days after the initial SAA visit. Of 7821 patients with the follow-up SAA visits within 60 days, most medical services provided were chlamydia testing (13.8%), gonorrhea testing (13.5%), syphilis testing (12.8%), HIV testing (14.0%); diagnosed anxiety (15.0%), and posttraumatic stress disorder (9.8%).

Conclusions

Current medical services during SAA visits for Medicaid patients are described in this evaluation. More collaboration with staff who handle SAA will improve SAA-related medical services.
HER2 IHC Expression and Gene Amplification in p53-aberrant High-grade Endometrial Endometrioid Carcinoma Suggests That This Population May Benefit From HER2 Testing and Targeted Therapy
Authors: Joehlin-Price Amy S. , Komforti Miglena K. , Ladwig Nicholas R. , Devine Patrick , Hoyle Carrie , McCoy Lauren , Sprague Cathy , Astbury Caroline , Hoda Raza , Chen Yunn-Yi , Garg Karuna
Published: March 2023

Among gynecologic cancers, uterine serous carcinoma (USC) has been shown to be human epidermal growth factor receptor 2 (HER2) amplified and trastuzumab has been included in the recent National Comprehensive Cancer Network (NCCN) guidelines for treatment of advanced stage or recurrent USC with HER2 overexpression/amplification. There is limited literature suggesting that a subset of high-grade endometrioid carcinomas with aberrant p53 expression may also be HER2 amplified and these patients could benefit from the addition of targeted therapy. We identified 59 p53-aberrant (mismatch repair proficient) FIGO 3 endometrioid carcinomas of the uterus. HER2 immunohistochemistry was performed in all 59 tumors and HER2 fluorescence in situ hybridization (FISH) was performed in 52 of the 59 cases. Four of the 59 cases were HER2 3+ by immunohistochemistry (6.7%), using the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) 2007, 2013, and 2018 criteria. HER2 FISH was performed in 3 of the 4 cases and was amplified in all 3. Nine, 8, and 7 tumors showed 2+ HER2 staining when applying 2018, 2013, and 2007 criteria, respectively, FISH was performed in 7 tumors and none were amplified. An additional 4 cases did not perfectly meet the 2018 ASCO/CAP criteria but were assigned a score of 2+, none were amplified by HER2 FISH. The remaining 42 cases showed 1+ or no staining for HER2, FISH was successfully performed in 38 tumors and none showed amplification. Approximately half of the tumors fulfilled criteria for HER2-low or HER2-very low (10 HER2-low and 20 HER2-very low). Our data shows that a subset of p53-aberrant high-grade endometrial endometrioid carcinoma express HER2 and these patients may benefit from the addition of targeted therapy. The role of targeted therapy in HER2-low gynecologic carcinoma is currently unexplored.
Factors associated with survival in patients with lymphoma and HIV
Authors: Vargas Juliano Cordova , Marques Mariana de Oliveira , Pereira Juliana , Braga Walter M. Tobias , Hamerschlak Nelson , Tabacof Jacques , Ferreira Paulo Roberto Abrão , Colleoni Gisele W. Braga , Baiocchi Otavio C.G.
Published: March 2023

Objective:

To analyze the factors associated with survival in the largest cohort of individuals with HIV and lymphoma so far described in Brazil.

Design:

A retrospective, observational, multicenter study involving five institutions in São Paulo, Brazil.

Methods:

The medical records of consecutive patients with HIV diagnosed with lymphoma between January 2000 and December 2019 were screened. Inclusion criteria consisted of age over 17 years and a biopsy-confirmed diagnosis of lymphoma. The data collected included age, sex, staging (Ann Arbor system), duration of HIV infection, CD4+ lymphocyte count, HIV viral load, lactate dehydrogenase, erythrocyte sedimentation rate and serum beta-2-microglobulin levels, treatment and outcome.

Results:

Overall, 276 patients were included. Median age was 42 years. Most patients were male (74.3%) and with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (28.6% and 46.4%, respectively). Most had non-Hodgkin lymphomas (89.2%, n = 246), particularly diffuse large B-cell lymphoma (40.9%) and Burkitt lymphoma (26.4%). Hodgkin lymphoma accounted for 9.4%. Advanced stages III/IV were predominant (86.8%). HIV viral load at the moment of lymphoma diagnosis was detectable in 52.9% of patients. A CD4+ cell count of <200 cells/μl was recorded for 53% of the patients. Most patients (62.4%) were on combination antiretroviral therapy. The factors that significantly affected survival were: the ECOG performance status, lymphoma subtype, staging, beta-2-microglobulin level, central nervous system (CNS) infiltration, site of CNS infiltration, relapsed/refractory lymphoma and International Prognostic Index score.

Conclusions:

HIV status, CD4+-lymphocyte count and relapsed/refractory disease affected survival. Rituximab did not appear to improve outcome in HIV-related lymphomas.
Prevalence of neurodevelopmental delays in infants with perinatal HIV infection in comparison with HIV exposure in rural South Africa
Authors: Rodriguez Violeta J. , Alfonso Demy , VanLandingham Hannah , Kozlova Sofia , Resch Zachary J. , Soble Jason R. , Jones Deborah L.
Published: March 2023

Background:

Assessing neurodevelopmental functioning in early infancy is essential as this is a critical period for infant development. Infants born to mothers with HIV are at a greater risk of developmental delays than those born to mothers without HIV. In this study, we analyzed differences in early neurodevelopmental functioning for infants with HIV exposure versus HIV infection to inform infant screening and early intervention.

Methods:

Participants were recruited from community health centers in Mpumalanga Province, South Africa. Prenatally, mothers completed baseline demographic assessment at 8 to 24-week gestation periods. Infant neurodevelopment was assessed using the Bayley Infant Neurodevelopmental Screener (BINS) 12 months postnatally. Five areas of development were assessed: cognition, receptive communication, expressive communication, fine motor ability, and gross motor ability.

Findings:

Postnatal infant assessment using the BINS revealed that infants were at risk for neurodevelopmental delays across all domains assessed. Notably, infants exposed to HIV, regardless of HIV status, were ‘at emerging risk’ or ‘at clear risk’ for cognitive (43.5%), receptive communication (38.2%), expressive communication (53.1%), fine motor (49.9%), and gross motor delays (55.6%). Differences were noted by HIV status in the cognition domain, such that HIV-exposed infants were more likely to be at emerging or clear risk than HIV-infected infants. There was a different trend with gross motor delays, such that HIV-infected infants were at a greater risk for motor delays than HIV-exposed, uninfected infants.

Conclusion:

Screening tools for this vulnerable population provide valuable early life assessment to determine infant needs for intervention and treatment planning. Such interventions may mitigate the impact of HIV status on neurodevelopmental health generally and cognition.
Modeling Family Medicine Provider Care Team Design to Improve Patient Care Continuity
Authors: Huang Yu-Li , Berg Bjorn P. , Lampman Michelle A. , Rushlow David R.
Published: March 2023

Background and Objectives:

Continuity of care is an integral aspect of high-quality patient care in primary care settings. In the Department of Family Medicine at Mayo Clinic, providers have multiple responsibilities in addition to clinical duties or panel management time (PMT). These competing time demands limit providers' clinical availability. One way to mitigate the impact on patient access and care continuity is to create provider care teams to collectively share the responsibility of meeting patients' needs.

Methods:

This study presents a descriptive characterization of patient care continuity based on provider types and PMT. Care continuity was measured by the percentage of patientappointmentsseen by a provider in theirowncareteam (ASOCT) with the aim of reducing the variability of provider care team continuity. The prediction method is iteratively developed to illustrate the importance of the individual independent components. An optimization model is then used to determine optimal provider mix in a team.

Results:

The ASOCT percentage in current practice among care teams ranges from 46% to 68% and the per team number of MDs varies from 1 to 5 while the number of nurse practitioners and physician assistants (NP/PAs) ranges from 0 to 6. The proposed methods result in the optimal provider assignment, which has an ASOCT percentage consistently at 62% for all care teams and 3 or 4 physicians (MDs) and NP/PAs in each care team.

Conclusions:

The predictive model combined with assignment optimization generates a more consistent ASOCT percentage, provider mix, and provider count for each care team.
PROPHYLACTIC nCMT-3 ATTENUATES SEPSIS-INDUCED ACUTE KIDNEY INJURY IN ASSOCIATION WITH NLRP3 INFLAMMASOME ACTIVATION AND APOPTOSIS
Authors: Ma Julia , Wang Xiaojing , Gu Raymond , Guo Dandan , Shi Changying , Kollisch-Singule Michaela , Suo Liye , Luo Juntao , Meng Qinghe , Cooney Robert N.
Published: March 2023

Background: The kidney is the most common extrapulmonary organ injured in sepsis. The current study examines the ability of aerosolized nanochemically modified tetracycline 3 (nCMT-3), a pleiotropic anti-inflammatory agent, to attenuate acute kidney injury (AKI) caused by intratracheal LPS. Methods: C57BL/6 mice received aerosolized intratracheal nCMT-3 (1 mg/kg) or saline, followed by intratracheal LPS (2.5 mg/kg) to induce acute lung injury–induced AKI. Tissues were harvested at 24 h. The effects of nCMT-3 and LPS on AKI were assessed by plasma/tissue levels of serum urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin, kidney injury molecule 1, and renal histology. Renal matrix metalloproteinase (MMP) level/activity, cytochrome C, Bax, Bcl-2, caspase-3, p38 mitogen-activated protein kinase activation, NLRP3, and caspase-1 were also measured. Apoptotic cells in kidney were determined by TUNEL assay. Renal levels of IL-1β and IL-6 were measured to assess inflammation. Results: Acute lung injury–induced AKI was characterized by increased plasma blood urea nitrogen, creatinine, injury biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule 1), and histologic evidence of renal injury. Lipopolysaccharide-treated mice demonstrated renal injury with increased levels of inflammatory cytokines (IL-1β, IL-6), active MMP-2 and MMP-9, proapoptotic proteins (cytochrome C, Bax/Bcl-2 ratio, cleaved caspase-3), apoptotic cells, inflammasome activation (NLRP3, caspase-1), and p38 signaling. Intratracheal nCMT-3 significantly attenuated all the measured markers of renal injury, inflammation, and apoptosis. Conclusions: Pretreatment with aerosolized nCMT-3 attenuates LPS-induced AKI by inhibiting renal NLRP3 inflammasome activation, renal inflammation, and apoptosis.
Tight Fit of the SIR Dynamic Epidemic Model to Daily Cases of COVID-19 Reported During the 2021-2022 Omicron Surge in New York City: A Novel Approach
Authors: Harris Jeffrey E.
Published: March 2023

We describe a novel approach to recovering the underlying parameters of the SIR dynamic epidemic model from observed data on case incidence. We formulate a discrete-time approximation to the original continuous-time model and search for the parameter vector that minimizes the standard least squares criterion function. We show that the gradient vector and matrix of second-order derivatives of the criterion function with respect to the parameters adhere to their own systems of difference equations and thus can be exactly calculated iteratively. Applying our new approach, we estimated a four-parameter SIR model from data on daily reported cases of COVID-19 during the SARS-CoV-2 Omicron/BA.1 surge of December 2021 - March 2022 in New York City. The estimated SIR model showed a tight fit to the observed data, but less so when we excluded residual cases attributable to the Delta variant during the initial upswing of the wave in December. Our analyses of both the real-world COVID-19 data and simulated case incidence data revealed an important problem of weak parameter identification. While our methods permitted separate estimation of the infection transmission parameter and the infection persistence parameter, only a linear combination of these two key parameters could be estimated with precision. The SIR model appears to be an adequate reduced-form description of the Omicron surge, but it is not necessarily the correct structural model. Prior information above and beyond case incidence data may be required to sharply identify the parameters and thus distinguish between alternative epidemic models.