bluuebunny/crossref_metadata_2025 huggingface dataset:
Strong correlation of maximal squat strength with sprint performance and vertical jump height in elite soccer players: Figure 1
Authors: Wisløff U , Castagna C , Helgerud J , Jones R , Hoff J
Published: May 2004

Background:A high level of strength is inherent in elite soccer play, but the relation between maximal strength and sprint and jumping performance has not been studied thoroughly.

Objective:To determine whether maximal strength correlates with sprint and vertical jump height in elite male soccer players.

Methods:Seventeen international male soccer players (mean (SD) age 25.8 (2.9) years, height 177.3 (4.1) cm, weight 76.5 (7.6) kg, and maximal oxygen uptake 65.7 (4.3) ml/kg/min) were tested for maximal strength in half squats and sprinting ability (0–30 m and 10 m shuttle run sprint) and vertical jumping height.

Result:There was a strong correlation between maximal strength in half squats and sprint performance and jumping height.

Conclusions:Maximal strength in half squats determines sprint performance and jumping height in high level soccer players. High squat strength did not imply reduced maximal oxygen consumption. Elite soccer players should focus on maximal strength training, with emphasis on maximal mobilisation of concentric movements, which may improve their sprinting and jumping performance.
Effects of prolonged strenuous exercise (marathon running) on biochemical and haematological markers used in the investigation of patients in the emergency department
Authors: Smith J E , Garbutt G , Lopes P , Pedoe D Tunstall
Published: May 2004

Objectives:To investigate the effects of strenuous exercise on commonly used biochemical and haematological variables in subjects running the 2002 London marathon.

Methods:34 healthy volunteers (7 female, 27 male) were recruited for the study. Blood was taken before the start (at registration) and immediately after completion of the marathon. Samples were analysed for urea and electrolytes, liver function tests, creatine kinase (CK), CK-MB isoenzyme, myoglobin, troponin I, full blood count, a clotting screen, and D-dimers. The results before and after exercise were compared. Pearson’s correlation coefficients were calculated for all variables.

Results:Significant increases were found in CK, CK-MB, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and myoglobin following the marathon. However, there was no significant change in the level of troponin I. There was also evidence of activation of the coagulation and fibrinolytic cascades following the marathon, with a reduction in activated partial thromboplastin time, a reduction in fibrinogen, and an increase in D-dimers.

Conclusions:The results confirm previous individual studies on marathon running and the biochemical and haematological tests routinely carried out in hospital. These are affected by prolonged exercise, and “abnormal” results in these tests may be normal after prolonged exercise and therefore not diagnostic of a disease process. The results of investigations in patients who have been exercising should be interpreted with caution.
Quadriceps atrophy: to what extent does it exist in patellofemoral pain syndrome?
Authors: Callaghan M J , Oldham J A
Published: May 2004

Background:Quadriceps atrophy is a commonly cited accompaniment to patellofemoral pain syndrome (PFPS), yet there is little valid, objective evidence for its existence.

Objective:To investigate atrophy and weakness of the quadriceps femoris muscle group in patients with PFPS using measures of cross-sectional area and peak extension torque.

Methods:A total of 57 patients with insidious onset of PFPS and 10 healthy control subjects had ultrasound scanning of the quadriceps femoris. The scans were analysed using computerised planimetry to estimate the cross-sectional area of the quadriceps femoris. Lower limb peak torque was also measured using a Biodex dynamometer.

Results:The mean of % differences revealed a 3.38% (95% confidence interval (CI) 1.3 to 5.45) difference in cross-sectional area (CSA) between the affected and unaffected limb in PFPS patients and a 1.31% (95% CI 0.06 to 2.55) difference in the dominant and non-dominant limb of the control group; the between-groups difference was not significant (p = 0.409). There was a 18.4% (95% CI 13 to 23.8) difference between the affected and unaffected limb in peak torque in PFPS patients and a 7.6% (95% CI 3.2 to 12) difference between the dominant and non-dominant limb in the control group; the between-groups difference was significant (p = 0.002).

Conclusions:The mean of % differences of 3.38% quadriceps atrophy between limbs was considerably less than the only other study using ultrasound scanning on the quadriceps in PFPS and was not significant between the groups. There were greater and more significant between-group differences in lower limb peak torque indicating that muscle strength may not be related to muscle size. These results help to re-appraise of the amount of quadriceps atrophy in PFPS.
Isolated first rib fracture in athletes
Authors: Sakellaridis T , Stamatelopoulos A , Andrianopoulos E , Kormas P
Published: May 2004

Isolated fractures of the first rib are uncommon. They are caused by major blunt trauma, a violent muscular pull, or fatigue. Diagnosis is usually made by chest radiography and computed tomography. Angiography is justified when certain criteria are met. Treatment is rest and mild analgesia. Early and late complications have been reported and are treated accordingly. The purpose of this article is to report a case of first rib stress fracture in a kick boxer and review the pertinent literature.
Treatment of spondylolysis with external electrical stimulation in young athletes: a critical literature review
Authors: Stasinopoulos D
Published: May 2004

Lumbar spondylolysis is a common cause of low back pain in adolescent athletes. It is a unilateral or bilateral defect of the pars interarticularis. The cause is still a matter of debate. A wide range of conservative treatments has been used. The purpose of this critical literature review is to investigate the efficacy of external electrical stimulation in the healing of this disorder.
SUPERSYMMETRIC MATRIX MODEL ON Z-ORBIFOLD
Authors: MIYAKE AKIKO
Published: May 2004

We find that the IIA matrix models defined on the non-compact C3/Z6, C2/Z2 and C2/Z4 orbifolds preserve supersymmetry where the fermions are on-mass-shell Majorana–Weyl fermions. In these examples supersymmetry is preserved both in the orbifolded space and in the non-orbifolded space at the same time. The matrix model on C3/Z6 orbifold has the same [Formula: see text] supersymmetry as the case of C3/Z3 orbifold which was pointed out previously. On the other hand the matrix models on C2/Z2 and C2/Z4 orbifold have a half of the [Formula: see text] supersymmetry. We further find that the matrix model on C2/Z2 orbifold with a parity-like identification preserves [Formula: see text] supersymmetry.
The “Normal” Endocrine Cell of the Gut: Changing Concepts and New Evidences
Authors: RINDI GUIDO , LEITER ANDREW B. , KOPIN ALAN S. , BORDI CESARE , SOLCIA ENRICO
Published: May 2004

Abstract: The endocrine cells of the gut are a highly specialized mucosal cell subpopulation. Within the gastrointestinal tract at least 14 different cell types produce a wide range of hormones with a specific regional distribution. The gut endocrine cells belong to the diffuse endocrine system. These cells present two regulated pathways of secretion characterized by large dense core vesicles (LDCV) and synaptic‐like microvesicles (SLMV). Gut endocrine cells are recognized by the expression of several “general” markers, including the LDCV marker chromogranin A and the SLMV marker synaptophysin, in addition to the cytosolic markers neuron‐specific enolase and protein gene product 9.5. The expression of different hormones identifies specific cell types. The gut endocrine cells are reputed to be terminally differentiated and incapable of proliferation. However, some data suggest that the number of gut endocrine cells may adapt in response to tissue‐specific physiological stimuli. Gut endocrine cell differentiation appears to follow a “constitutive” tissue‐specific pathway, which may be disrupted and investigated by genetic manipulation in mice. It is suggested that endocrine cell homeostasis is maintained by the entry of new endocrine‐committed cells along the differentiation pathway and that such intermediate cells may be sensitive to physiological stimuli as well as transforming agents.
Molecular Imaging of Tumor Angiogenesis
Authors: SCHIRNER MICHAEL , MENRAD ANDREAS , STEPHENS ANDREW , FRENZEL THOMAS , HAUFF PETER , LICHA KAI
Published: May 2004

Abstract: Advances in imaging provide new insights into the pathophysiol‐ogy of many diseases. Established imaging technologies such as MRI, CT, PET, and ultrasound are routinely applied to determine features of tumor blood vessels that distinguish them from normal blood vessels. These techniques yield information on blood flow, blood volume, and vessel permeability. Often, an intravenously injected imaging contrast agent without affinity to a specific target structure is applied to enable detection of malignant lesions. One of the emerging innovations in diagnostic imaging is the evolution of molecular imaging techniques. Molecular imaging is a noninvasive approach to determine the expression of indicative marker molecules of the tumor angiogenesis process. Meanwhile, this approach has been established for all imaging modalities and may further improve sensitivity of diagnostic tumor imaging. Another goal is to provide information with respect to drug treatment monitoring and therapeutic vascular targeting strategies.
Liver Transplantation for Treatment of Metastatic Neuroendocrine Tumors
Authors: AHLMAN HÅKAN , FRIMAN STYRBJÖRN , CAHLIN CHRISTIAN , NILSSON OLA , JANSSON SVANTE , WÄNGBERG BO , OLAUSSON MICHAEL
Published: May 2004

Abstract: Liver transplantation can be considered a therapeutic option for patients with neuroendocrine tumors only metastatic to the liver. Important selection criteria are well‐differentiated tumors and a low proliferation rate (Ki67 <10%). In this series, orthopic liver transplantation offered good relief of symptoms and long disease‐free intervals with initial survival of grafts and patients as in benign disease. The experience with multivisceral transplantation is still limited.
Computer-Aided Complexity Classification of Dial-a-Ride Problems
Authors: de Paepe Willem E. , Lenstra Jan Karel , Sgall Jiri , Sitters René A. , Stougie Leen
Published: May 2004

In dial-a-ride problems, items have to be transported from a source to a destination. The characteristics of the servers involved as well as the specific requirements of the rides may vary. Problems are defined on some metric space, and the goal is to find a feasible solution that minimizes a certain objective function. The structure of these problems allows for a notation similar to the standard notation for scheduling and queueing problems. We introduce such a notation and show how a class of 7,930 dial-a-ride problem types arises from this approach. In examining their computational complexity, we define a partial ordering on the problem class and incorporate it in the computer program DARCLASS. As input DARCLASS uses lists of problems whose complexity is known. The output is a classification of all problems into one of three complexity classes: solvable in polynomial time, NP-hard, or open. For a selection of the problems that form the input for DARCLASS, we exhibit a proof of polynomial-time solvability or NP-hardness.
Potential Anaphylactic Shock with Abciximab Readministration
Authors: Pharand Chantal , Palisaitis Donald A. , Hamel Denis
Published: May 2004

A 46‐year‐old woman developed an anaphylactic reaction during percutaneous coronary intervention after she was pretreated with prednisone and diphenhydramine for a known allergy to iodine. She developed pruritus, edema, and nausea, which were followed by bradycardia and shock, minutes after administration of a bolus and standard‐dose infusion of abciximab. The reaction was treated successfully with epinephrine, methoxamine, hydrocortisone, atropine, furosemide, sodium bicarbonate, diphenhydramine, and ranitidine.
Intravenous Cyclosporine‐Rifampin Interaction in a Pediatric Bone Marrow Transplant Recipient
Authors: Zelunka Elyse J.
Published: May 2004

A 10‐year‐old girl with chronic myelogenous leukemia began receiving cyclosporine the day before bone marrow transplant surgery. Three days after the transplant, she developed fever and neutropenia due to a Staphylococcus aureus bacteremia. Despite treatment with various antibiotics, the patient's fever persisted over the next 4 days. Intravenous rifampin was added to her antibiotic regimen of piperacillin, tobramycin, cloxacillin, and amphotericin. On day 12, the patient's blood cultures were negative and her fever had resolved; rifampin was discontinued. On day 16, the patient engrafted; she subsequently developed a grade II graft‐versus‐host disease of the skin and gastrointestinal tract, which responded to methylprednisolone. Her cyclosporine blood levels, which had been subtherapeutic since day 5 despite increasing intravenous dosages, were within the therapeutic range on day 21, and she was discharged 12 days later. To our knowledge, this is the first documented case of an intravenous cyclosporine‐rifampin interaction that resulted in subtherapeutic cyclosporine concentrations in a child receiving a bone marrow transplant who subsequently developed acute graft‐versus‐host disease.
Levofloxacin Treatment Failure in a Patient with Fluoroquinolone‐Resistant Streptococcus pneumoniae Pneumonia
Authors: Kays Michael B. , Smith David W. , Wack Matthew F. , Denys Gerald A.
Published: May 2004

The frequency of fluoroquinolone‐resistant Streptococcus pneumoniae has increased as fluoroquinolone administration for treatment of respiratory tract infections has increased. Levofloxacin treatment failed in a patient who had pneumococcal pneumonia and had received three previous courses of levofloxacin therapy. Susceptibility testing revealed high‐level resistance to levofloxacin (minimum inhibitory concentration [MIC] > 32 μg/ml), and cross‐resistance to moxifloxacin (MIC 4 μg/ml), trovafloxacin (6 μg/ml), and gatifloxacin (12 μg/ml). Sequencing of the quinolone‐resistance determining region revealed a mutation of serine‐81 to phenylalanine (Ser81→Phe) in the gyrA region of DNA gyrase and a Ser79→Phe mutation in the parC region of topoisomerase IV. The patient was treated successfully with intravenous ceftriaxone followed by oral cefprozil. Clinicians must be aware of local resistance patterns and the potential for fluoroquinolone treatment failures in patients with infections caused by S. pneumoniae.
Pharmacokinetic and Pharmacodynamic Evaluation of Two Dosing Regimens for Piperacillin‐Tazobactam
Authors: Kim Myo‐Kyoung , Capitano Blair , Mattoes Holly M. , Xuan Dawei , Quintiliani Richard , Nightingale Charles H. , Nicolau David P.
Published: May 2004

Study Objective. To compare the pharmacokinetic and pharmacodynamic profiles of two dosing regimens for piperacillin‐tazobactam against commonly encountered pathogens. The regimens compared were piperacillin 4.0 g‐tazobactam 0.5 g administered every 8 hours, and piperacillin 3.0 g‐tazobactam 0.375 g administered every 6 hours.

Design. Multiple‐dose, open‐label, randomized, crossover study.

Setting. Clinical research center at Hartford Hospital.

Subjects. Twelve healthy volunteers.

Intervention. The two dosing regimens for piperacillin‐tazobactam were administered intravenously in crossover design. Blood was sampled after the third dose.

Measurements and Main Results. Drug concentrations were determined by a validated high‐performance liquid chromatography assay. The percentage of time above minimum inhibitory concentration (%T>MIC) for piperacillin was calculated for a range of MIC values. The maximum concentration (Cmax), area under the concentration‐time curve (AUC0‐τ), and total clearance of piperacillin differed significantly between the two study regimens, as did the Cmax, AUC0‐τ, volume of distribution, and total clearance of tazobactam (p<0.05). The piperacillin 4.0 g‐tazobactam 0.5 g regimen provided 40–50% T>MIC for MIC values 8–16 μg/ml; a similar value for the piperacillin 3.0 g‐tazobactam 0.375 g regimen was 16–32 μg/ml.

Conclusion. Although statistically significant differences in the pharmaco‐dynamic profile were noted for the regimens, both provide adequate T>MIC against commonly encountered pathogens considered susceptible to piperacillin‐tazobactam. However, for treatment of Pseudomonas aeruginosa infection, combination therapy or higher‐dosage regimens (e.g., piperacillin 3.0 g‐tazobactam 0.375 g every 4 hours, piperacillin 4.0 g‐tazobactam 0.5 g every 6 hours, or continuous‐infusion piperacillin 12 g‐tazobactam 1.5 g/day) may be a prudent option when full MIC data are unavailable.
Risk of Clinical Blood Dyscrasia in a Cohort of Antibiotic Users
Authors: Huerta Consuelo , Rodríguez Luis Alberto García
Published: May 2004

Blood dyscrasias, although rare, can be fatal. Many drugs, including antibiotics, are associated with these dyscrasias. We conducted a cohort study with a nested case‐control analysis using data from the General Practice Research Database to estimate incidence rates of clinical blood dyscrasias in the general population and to examine their association with use of antibiotic drugs. The study population consisted of patients aged 5–69 years receiving at least one antibiotic prescription from January 1994‐September 1998. The final cohort consisted of 822,048 persons who received 1,507,307 antibiotic prescriptions during the study period. The main outcome measure was a diagnosis of neutropenia, agranulocytosis, hemolytic anemia, thrombocytopenia, bicytopenia, pancytopenia, or aplastic anemia. We confirmed 122 patients who developed clinical blood dyscrasias. The incidence was 3.3/100,000 person‐years in the general population. Patients older than 60 years (relative risk [RR] 2.8, 95% confidence interval [CI] 1.6–5.0) and those who took phenothiazines (RR 49.0, 95% CI 4.9–488.2) had an increased risk of blood dyscrasia. Users of antibiotics had an RR of 4.4 (95% CI 2.6–7.5), and patients taking more than one class of antibiotics had an RR of 29.1 (95% CI 9.1–92.8). Among individual antibiotic classes, the greatest risk was with cephalosporins (RR 13.8, 95% CI 3.6–52.6). Although uncommon, our study supports an association between blood dyscrasias and antibiotics.
Hypercalcemia Induced by 13‐cis‐Retinoic Acid in a Patient with Neuroblastoma
Authors: Belden Tara L. , Ragucci Dominic P.
Published: May 2004

Hypercalcemia is a potential dosage‐related adverse effect of 13‐cis‐retinoic acid in patients with neuroblastoma. Severe hypercalcemia requiring dosage reduction has been reported in children receiving 13‐cis‐retinoic acid 200 mg/m2/day and in those with concurrent renal impairment receiving 160 mg/m2/day. A 12‐year‐old girl without renal dysfunction, diagnosed with neuroblastoma, developed severe hypercalcemia requiring several hospitalizations while receiving 13‐cis‐retinoic acid 160 mg/m2/day. Her hypercalcemia resolved with hydration, diuretic therapy, and temporary discontinuation of 13‐cis‐retinoic acid. Despite a 50% dosage reduction to 80 mg/m2/day, severe hypercalcemia recurred with the next treatment cycle. Further treatment with 13‐cis‐retinoic acid was made tolerable by shortening the duration of the remaining cycles. Serum calcium levels should be monitored in patients with neuroblastoma who receive 13‐cis‐retinoic acid.
Hemolysis as a Potential Complication of Acetaminophen Overdose in a Patient with Glucose‐6‐Phosphate Dehydrogenase Deficiency
Authors: Sklar Grant E.
Published: May 2004

A 21‐year‐old Chinese man who took an overdose of acetaminophen was hospitalized. His medical history was significant for glucose‐6‐phosphate dehydrogenase (G6PD) deficiency. On admission, physical examination was unremarkable and laboratory results were within normal limits. During his hospitalization, the patient experienced a decrease in hemoglobin concentration of almost 4 g/dl and an increase in unconjugated bilirubin consistent with the development of hemolysis. Acetaminophen was the most likely cause of the hemolysis. Clinicians must be aware of this potential complication after acetaminophen overdose in G6PD‐deficient patients.
Human Immunodeficiency Viruses and Drug Therapy: Resistance and Implications for Antiretroviral Therapy
Authors: Idemyor Vincent
Published: May 2004

Through a concerted effort to combat the human immunodeficiency virus (HIV) epidemic, researchers have made significant strides in molecular biology, virology, and immunology, which have resulted in an increased understanding of the complexities of this infection. The biggest obstacle to the success of current HIV therapy, however, is the emergence of viral resistance. Viral resistance is caused by mutations in the HIV‐1 genome coding for structural changes in the target enzymes that can affect the binding or activity of the inhibitors. More information on the genetic basis of HIV resistance, mechanisms of viral variation, and therapeutic strategies for overcoming HIV resistance are needed. Sixty million people have been infected with HIV, 24 million have died, and it is projected that 200 million individuals will be infected by 2020.
Macrolide Therapy for Chlamydia pneumoniae in the Secondary Prevention of Coronary Artery Disease: A Meta‐Analysis of Randomized Controlled Trials
Authors: Etminan Mahyar , Carleton Bruce , Delaney J. A. C. , Padwal Raj
Published: May 2004

Study Objective. As recent studies have shown that antibiotic therapy to eradicate Chlamydia pneumoniae may be beneficial in the secondary prevention of coronary artery disease, and studies to date may have lacked statistical power, we conducted a meta‐analysis of randomized controlled trials to determine the role of antibiotic therapy in this patient population.

Design. Systematic review and meta‐analysis of randomized controlled trials.

Patients. A total of 12,032 patients from nine studies.

Measurements and Main Results. We searched MEDLINE, EMBASE, the Cochrane Controlled Trials Register, and abstracts of conference proceedings to identify pertinent studies. The random effects model was used to estimate a pooled relative risk. Heterogeneity was assessed using the bootstrap version of the Q statistic with 1000 replications. In total, we reviewed nine randomized controlled trials enrolling 12,032 patients; six enrolled patients with acute coronary syndrome, two enrolled patients with stable coronary artery disease, and one enrolled a mixed population. Compared with placebo, macrolide therapy was not associated with a significant reduction in any coronary event (relative risk [RR] 0.98, 95% confidence interval [CI] 0.88–1.08), myocardial infarction or angina (RR 0.89, 95% CI 0.68–1.16), or overall mortality (RR 0.95, 95% CI 0.81–1.12).

Conclusion. Our results do not support routine use of antichlamydial therapy for secondary prevention of coronary events.
Greater Effect of Enhanced Pharmacist Care on Cholesterol Management in Patients with Diabetes Mellitus: A Planned Subgroup Analysis of the Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP)
Authors: Simpson Scot H. , Johnson Jeffrey A. , Biggs Rosemarie S. , Tsuyuki Ross T.
Published: May 2004

Study Objective. To determine the effect of enhanced pharmacist care on cholesterol management in patients with and without diabetes mellitus.

Methods. We conducted a planned subgroup analysis of the Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP), a 54‐center randomized trial of pharmacist intervention compared with usual care in patients at high risk for cardiovascular events. The patients involved had atherosclerotic disease or diabetes. We compared the effect of pharmacist intervention in patients with and without diabetes. The primary end point was a composite of performing a fasting cholesterol profile, or adding or increasing the dosage of a cholesterol‐lowering drug. Secondary end points were individual components of the primary end point and change in 10‐year risk for cardiovascular events, using the Framingham risk equation.

Results. Of the 675 patients enrolled in the SCRIP study, 294 (44%) had diabetes. Enhanced pharmacist care had a more beneficial effect on cholesterol management in those with diabetes (odds ratio [OR] 4.8) than without diabetes (OR 2.1), p=0.01. Secondary end points showed similar trends, and reduction in Framingham risk was greater in patients with diabetes than without.

Conclusion. Pharmacist intervention for dyslipidemia appears to have a greater impact in patients with diabetes. Results of this substudy suggest that pharmacists should target this patient group for interventions in cholesterol risk management.
Tenofovir‐Related Nephrotoxicity: Case Report and Review of the Literature
Authors: James Christopher W. , Steinhaus Mary C. , Szabo Susan , Dressler Robert M.
Published: May 2004

Tenofovir is a nucleotide reverse transcriptase inhibitor for treatment of human immunodeficiency virus (HIV) infection. Several cases of renal failure associated with tenofovir therapy recently have been reported. A 54‐year‐old man with HIV experienced decreasing renal function and Fanconi's syndrome secondary to tenofovir therapy. His condition gradually improved after discontinuation of the drug. The available medical literature for reported cases of tenofovir‐related nephrotoxicity indicates that this complication is apparently rare. However, our case report and literature review underscore the importance of monitoring renal function when treating patients with any nucleotide reverse transcriptase inhibitor.
Availability of Mental Telehealth Services in the US
Authors: Cantor Jonathan , Schuler Megan S. , Matthews Samantha , Kofner Aaron , Breslau Joshua , McBain Ryan K.
Published: February 2024

Importance

Telehealth utilization for mental health care remains much higher than it was before the COVID-19 pandemic; however, availability may vary across facilities, geographic areas, and by patients’ demographic characteristics and mental health conditions.

Objective

To quantify availability, wait times, and service features of telehealth for major depressive disorder, general anxiety disorder, and schizophrenia throughout the US, as well as facility-, client-, and county-level characteristics associated with telehealth availability.

Design, Settings, and Participants

Cross-sectional analysis of a secret shopper survey of mental health treatment facilities (MHTFs) throughout all US states except Hawaii from December 2022 and March 2023. A nationally representative sample of 1938 facilities were contacted; 1404 (72%) responded and were included. Data analysis was performed from March to July 2023.

Exposure

Health facility, client, and county characteristics.

Main Outcome and Measures

Clinic-reported availability of telehealth services, availability of telehealth services (behavioral treatment, medication management, and diagnostic services), and number of days until first telehealth appointment. Multivariable logistic and linear regression analyses were conducted to assess whether facility-, client-, and county-level characteristics were associated with each outcome.

Results

Of the 1221 facilities (87%) accepting new patients, 980 (80%) reported offering telehealth. Of these, 97% (937 facilities) reported availability of counseling services; 77% (726 facilities), medication management; and 69% (626 facilities) diagnostic services. Telehealth availability did not differ by clinical condition. Private for-profit (adjusted odds ratio [aOR], 1.75; 95% CI, 1.05-2.92) and private not-for-profit (aOR, 2.20; 95% CI, 1.42-3.39) facilities were more likely to offer telehealth than public facilities. Facilities located in metropolitan counties (compared with nonmetropolitan counties) were more likely to offer medication management services (aOR, 1.83; 95% CI, 1.11-3.00) but were less likely to offer diagnostic services (aOR, 0.67; 95% CI, 0.47-0.95). Median (range) wait time for first telehealth appointment was 14 (4-75) days. No differences were observed in availability of an appointment based on the perceived race, ethnicity, or sex of the prospective patient.

Conclusions and Relevance

The findings of this cross-sectional study indicate that there were no differences in the availability of mental telehealth services based on the prospective patient’s clinical condition, perceived race or ethnicity, or sex; however, differences were found at the facility-, county-, and state-level. These findings suggest widespread disparities in who has access to which telehealth services throughout the US.
Verification of molecular subtyping of bladder cancer in the GUSTO clinical trial
Authors: Griffin Jon , Down Jenny , Quayle Lewis A , Heath Paul R , Gibb Ewan A , Davicioni Elai , Liu Yang , Zhao Xin , Swain Jayne , Wang Dennis , Hussain Syed , Crabb Simon , Catto James WF ,   the GUSTO Trial Management Group
Published: February 2024

The GUSTO clinical trial (Gene expression subtypes of Urothelial carcinoma: Stratified Treatment and Oncological outcomes) uses molecular subtypes to guide neoadjuvant therapies in participants with muscle‐invasive bladder cancer (MIBC). Before commencing the GUSTO trial, we needed to determine the reliability of a commercial subtyping platform (Decipher Bladder; Veracyte) when performed in an external trial laboratory as this has not been done previously. Here, we report our pre‐trial verification of the TCGA molecular subtyping model using gene expression profiling. Formalin‐fixed paraffin‐embedded tissue blocks of MIBC were used for gene expression subtyping by gene expression microarrays. Intra‐ and inter‐laboratory technical reproducibilities, together with quality control of laboratory and bioinformatics processes, were assessed. Eighteen samples underwent analysis. RNA of sufficient quality and quantity was successfully extracted from all samples. All subtypes were represented in the cohort. Each sample was subtyped twice in our laboratory and once in a separate reference laboratory. No clinically significant discordance in subtype occurred between intra‐ or inter‐laboratory replicates. Examination of sample histopathology showed variability of morphological appearances within and between subtypes. Overall, these results show that molecular subtyping by gene expression profiling is reproducible, robust and suitable for use in the GUSTO clinical trial.
Injectable and Thermosensitive Hydrogel with Platelet‐Rich Plasma for Enhanced Biotherapy of Skin Wound Healing
Authors: Liu Gengjun , Yang Yuanming , Liu Yan , Li Ying , Jiang Mingyuan , Li Yaxin , Meng Zifan , Zhao Zhen , Liu Zheng , Liu Jiao , Ge Dongmei , Wang Haiyan
Published: February 2024

The rapid and effective healing of skin wounds resulted from severe injuries and full‐layer skin defects remains a pressing clinical challenge in contemporary medical practice. The reduction of wound infection and rapid healing is helpful to rebuild and repair skin tissue. Here, a thermosensitive chitosan‐based wound dressing hydrogel incorporating β‐glycerophosphate (GP), hydroxy propyl cellulose (HPC), graphene oxide (GO), and platelet‐rich plasma (PRP) is developed, which exhibits the dual functions of antibacterial properties and repair promotion. GP and HPC enhance the mechanical properties through forming hydrogen bonding connection, while GO produces local heat under near‐infrared light, leading to improved blood circulation and skin recovery. Notably, antibacterial properties against Pseudomonas aeruginosa, and control–release of growth factors from PRP are also achieved based on the system. In vitro experiments reveal its biocompatibility, and ability to promote cell proliferation and migration. Animal experiments demonstrate that the epithelial repair and collagen deposition can be promoted during skin wound healing in Sprague Dawley rats. Moreover, a reduction in wound inflammation levels and the improvement of wound microenvironment are observed, collectively fostering effective wound healing. Therefore, the composite hydrogel system incorporated with GO and PRP can be a promising dressing for the treatment of skin wounds.
Smart Design of ZnFe and ZnFe@Fe Nanoparticles for MRI‐Tracked Magnetic Hyperthermia Therapy: Challenging Classical Theories of Nanoparticles Growth and Nanomagnetism
Authors: Caro Carlos , Guzzi Cinzia , Moral‐Sánchez Irene , Urbano‐Gámez Jesús David , Beltrán Ana M. , García‐Martín Maria Luisa
Published: February 2024

Iron Oxide Nanoparticles (IONPs) hold the potential to exert significant influence on fighting cancer through their theranostics capabilities as contrast agents (CAs) for magnetic resonance imaging (MRI) and as mediators for magnetic hyperthermia (MH). In addition, these capabilities can be improved by doping IONPs with other elements. In this work, the synthesis and characterization of single‐core and alloy ZnFe novel magnetic nanoparticles (MNPs), with improved magnetic properties and more efficient magnetic‐to‐heat conversion, are reported. Remarkably, the results challenge classical nucleation and growth theories, which cannot fully predict the final size/shape of these nanoparticles and, consequently, their magnetic properties, implying the need for further studies to better understand the nanomagnetism phenomenon. On the other hand, leveraging the enhanced properties of these new NPs, successful tumor therapy by MH is achieved following their intravenous administration and tumor accumulation via the enhanced permeability and retention (EPR) effect. Notably, these results are obtained using a single low dose of MNPs and a single exposure to clinically suitable alternating magnetic fields (AMF). Therefore, as far as the authors are aware, for the first time, the successful application of intravenously administered MNPs for MRI‐tracked MH tumor therapy in passively targeted tumor xenografts using clinically suitable conditions is demonstrated.
Targeted Macrophage CRISPR‐Cas13 mRNA Editing in Immunotherapy for Tendon Injury
Authors: Wang Shuo , Xiao Yao , Tian Jian , Dai Bo , Tao Zaijin , Liu Jingwen , Sun Zhenyu , Liu Xuanzhe , Li Yanhao , Zhao Gang , Cui Yong , Wang Fei , Liu Shen
Published: February 2024

CRISPR‐Cas13 holds substantial promise for tissue repair through its RNA editing capabilities and swift catabolism. However, conventional delivery methods fall short in addressing the heightened inflammatory response orchestrated by macrophages during the acute stages of tendon injury. In this investigation, macrophage‐targeting cationic polymers are systematically screened to facilitate the entry of Cas13 ribonucleic‐protein complex (Cas13 RNP) into macrophages. Notably, SPP1 (OPN encoding)‐producing macrophages are recognized as a profibrotic subtype that emerges during the inflammatory stage. By employing ROS‐responsive release mechanisms tailored for macrophage‐targeted Cas13 RNP editing systems, the overactivation of SPP1 is curbed in the face of an acute immune microenvironment. Upon encapsulating this composite membrane around the tendon injury site, the macrophage‐targeted Cas13 RNP effectively curtails the emergence of injury‐induced SPP1‐producing macrophages in the acute phase, leading to diminished fibroblast activation and mitigated peritendinous adhesion. Consequently, this study furnishes a swift RNA editing strategy for macrophages in the inflammatory phase triggered by ROS in tendon injury, along with a pioneering macrophage‐targeted carrier proficient in delivering Cas13 into macrophages efficiently.
Copper‐Catalyzed Sequential C(sp2)−H/C(sp3)−H Annulation of Indoles with Propargylic Alcohols to Access Hydrobenzo[b]carbazoles
Authors: Zhang Yi‐Rui , Qiu Zong‐Wang , Fu Zhao‐Jie , Chen Shao‐Shuai , Pan Han‐Peng , Qiong Li Bao , Ma Ai‐Jun , Zhang Xiang‐Zhi
Published: February 2024

Herein, we describe a copper‐catalyzed sequential C(sp2)−H/C(sp3)−H annulation of indoles with propargylic alcohols for the synthesis of diversely functionalized hydrobenzo[b]carbazole scaffolds. The reaction involves a Friedel‐Crafts addition, 1,5‐H shift, 6π electrocyclization, and dearomatization‐aromatization cascade. Importantly, this is a report of the use of 2‐(diarylmethyl)indoles as three‐carbon synthons in a (3+3) annulation reaction involving C(sp3)−H indole functionalization under oxidant‐free conditions.
An Amphibious Fully‐Soft Centimeter‐Scale Miniature Crawling Robot Powered by Electrohydraulic Fluid Kinetic Energy
Authors: Xiong Quan , Zhou Xuanyi , Li Dannuo , Ambrose Jonathan William , Yeow Raye Chen‐Hua
Published: February 2024

Miniature locomotion robots with the ability to navigate confined environments show great promise for a wide range of tasks, including search and rescue operations. Soft miniature locomotion robots, as a burgeoning field, have attracted significant research interest due to their exceptional terrain adaptability and safety features. Here, a fully‐soft centimeter‐scale miniature crawling robot directly powered by fluid kinetic energy generated by an electrohydraulic actuator is introduced. Through optimization of the operating voltage and design parameters, the average crawling velocity of the robot is dramatically enhanced, reaching 16 mm s−1. The optimized robot weighs 6.3 g and measures 5 cm in length, 5 cm in width, and 6 mm in height. By combining two robots in parallel, the robot can achieve a turning rate of ≈3° s−1. Additionally, by reconfiguring the distribution of electrodes in the electrohydraulic actuator, the robot can achieve 2 degrees‐of‐freedom translational motion, improving its maneuverability in narrow spaces. Finally, the use of a soft water‐proof skin is demonstrated for underwater locomotion and actuation. In comparison with other soft miniature crawling robots, this robot with full softness can achieve relatively high crawling velocity as well as increased robustness and recovery.
Double‐Walled Tubular Heusler‐Type Platinum–Ruthenium Phosphide as All‐pH Hydrogen Evolution Reaction Catalyst Outperforming Platinum and Ruthenium
Authors: Hong Yongju , Cho Seong Chan , Kim Soobean , Jin Haneul , Seol Jae Hun , Lee Tae Kyung , Ryu Jong‐kyeong , Tomboc Gracita M. , Kim Taekyung , Baik Hionsuck , Choi Changhyeok , Jo Jinhyoung , Jeong Sangyeon , Lee Eunsoo , Jung Yousung , Ahn Docheon , Kim Yong‐Tae , Yoo Sung Jong , Lee Sang Uck , Lee Kwangyeol
Published: February 2024

Nanostructured ionic compounds have driven major technological advancements in displays, photovoltaics, and catalysis. Current research focuses on refining the chemical composition of such compounds. In this study, a strategy for creating stoichiometrically well‐defined nanoscale multiple‐cation systems, where the atomically precise structure maximizes the synergistic cooperation between cations at the atomic scale is reported. The unprecedented construction of Heusler‐type PtRuP2 double‐walled nanotubes through sequential anion/cation exchange reactions is demonstrated. The PtRuP2 catalyst exhibits record‐high catalytic performance and durability for the hydrogen evolution reaction (HER) in alkaline electrolytes and anion‐exchange membrane water electrolyzers. The investigations highlight the crucial role of Pt/Ru dual centers, providing multiple active sites that accelerate the HER kinetics within a single phosphide material, in the sequential operation of H2O activation/dissociation at Ru and H2 production at adjacent Pt sites. These findings open new avenues for optimizing ionic compound‐based HER electrocatalysts, offering platinum‐metal alternatives in acidic and alkaline media.
Genetic consequences of Last Glacial–Holocene changes in snowfall regime in Arnica mallotopus populations: A plant confined to heavy‐snow areas of Japan
Authors: Masuda Kazutoshi , Setoguchi Hiroaki , Nagasawa Koki , Hirota Shun K. , Suyama Yoshihisa , Sawa Kazuhiro , Fukumoto Shigeru , Ishihara Masae I. , Abe Harue , Tsuboi Hayato , Tango Tsuguoki , Mori Sayoko , Sakaguchi Shota
Published: February 2024

Premise

Snow is an important environmental factor affecting plant distribution. Past changes in snowfall regimes may have controlled the demographies of snow‐dependent plants. However, our knowledge of changes in the distribution and demographies of such plants is limited because of the lack of fossil records.

Methods

Population genetic and landscape genetic analyses were used to investigate the response of population dynamics of Arnica mallotopus (Asteraceae)—a plant confined to heavy‐snow areas of Japan—to changes in snowfall regimes from the Last Glacial Period to the Holocene.

Results

The population genetic analysis suggested that the four geographic lineages diverged during the Last Glacial Period. The interaction between reduced snowfall and lower temperatures during this period likely triggered population isolation in separate refugia. Subpopulation differentiation in the northern group was lower than in the southern group. Our ecological niche model predicted that the current distribution was patchy in the southern region; that is, the populations were isolated by topologically flat and climatically unsuitable lowlands. The landscape genetic analysis suggested that areas with little snowfall acted as barriers to the Holocene expansion of species distribution and continued limiting gene flow between local populations.

Conclusions

These findings indicate that postglacial population responses vary among regions and are controlled by environmental and geographic factors. Thus, changes in snowfall regime played a major role in shaping the distribution and genetic structure of the snow‐dependent plant.
Aggressive T‐cell lymphomas: 2024: Updates on diagnosis, risk stratification, and management
Authors: Ong Shin Yeu , Zain Jasmine M.
Published: February 2024

Introduction

Aggressive T‐cell lymphomas continue to have a poor prognosis. There are over 30 different subtypes of peripheral T‐cell lymphoma (PTCL), and we are now beginning to understand the differences between the various subtypes beyond histologic variations.

Molecular Pathogenesis of Various Subtypes of PTCL

Gene expression profiling and other molecular techniques have enabled deeper understanding of differences in various subtypes as reflected in the latest 5th WHO classification of PTCL. It is becoming increasingly clear that therapeutic approaches that target specific cellular pathways are needed to improve the clinical outcomes of PTCL.

Targeted Therapies

There are many targeted agents currently in various stages of clinical trials for PTCL that take advantage of the differential expression of specific proteins or receptors in PTCL tumors. This includes the CD30 directed antibody drug conjugate brentuximab vedotin. Other notable targets are phosphatidylinositol 3‐kinase inhibitors, histone deacetylase inhibitors, CD25, and chemokine receptor 4. Anaplastic lymphoma kinase (ALK) inhibitors are promising for ALK expressing tumors.

Immunotherapies

Allogeneic stem cell transplant continues to be the curative therapy for most aggressive subtypes of PTCL. The use of checkpoint inhibitors in the treatment of PTCL is still controversial, with best results seen in cases of extranodal natural killer cell/T‐cell lymphoma. Bispecific antibody‐based treatments and chimeric antigen receptor cell‐based therapies are in clinical trials.
Variation of thoracolumbar vertebral morphology in anthropoid primates
Authors: Kinoshita Yuki , Hirasaki Eishi
Published: February 2024

Objectives

Morphological variation among extant primates in the lumbar vertebral column is well studied. However, knowledge concerning the thoracic spine, an important region responsible for supporting and facilitating movement in the upper trunk, remains relatively scarce. Consequently, our comprehension of the functional differentiation exhibited throughout the thoracolumbar vertebral column among various primate species remains constrained. In this study, we examined patterns of morphological variation in the thoracolumbar vertebral column of extant hominoids, cercopithecoids, and Ateles.

Materials and Methods

We collected external shape data on 606 thoracic and lumbar vertebrae from Homo sapiens, Pan troglodytes, Hylobates lar, Macaca fuscata, Chlorocebus aethiops, Colobus guereza, Ateles geoffroyi, and A. belzebuth. Forty‐four landmarks were obtained on the three‐dimensional surface. Geometric morphometrics was used to quantify the centroid size and variation of the shapes of thoracic and lumbar vertebrae.

Results

Cercopithecoids exhibited greater variation in the size and shape of their thoracic and lumbar vertebrae compared to hominoids and Ateles. Although many vertebral features contributed to the observed variation throughout the thoracolumbar vertebral column within the taxon, the transverse and spinous processes exhibited relatively major contributions.

Discussion

Our results suggest that quadrupedal locomotion requires the functional differentiation between thoracic and lumbar vertebrae, and for hominoids, functional adaptation to orthograde posture necessitates a relatively more uniform shape of thoracic and lumbar vertebrae.
Astroglial activation: Current concepts and future directions
Authors: Edison Paul
Published: February 2024

Astrocytes are abundantly and ubiquitously expressed cell types with diverse functions throughout the central nervous system. Astrocytes show remarkable plasticity and exhibit morphological, molecular, and functional remodeling in response to injury, disease, or infection of the central nervous system, as evident in neurodegenerative diseases. Astroglial mediated inflammation plays a prominent role in the pathogenesis of neurodegenerative diseases. This review focus on the role of astrocytes as essential players in neuroinflammation and discuss their morphological and functional heterogeneity in the normal central nervous system and explore the spatial and temporal variations in astroglial phenotypes observed under different disease conditions. This review discusses the intimate relationship of astrocytes to pathological hallmarks of neurodegenerative diseases. Finally, this review considers the putative therapeutic strategies that can be deployed to modulate the astroglial functions in neurodegenerative diseases.

Highlights

Astroglia mediated neuroinflammation plays a key role in the pathogenesis of neurodegenerative diseases.

Activated astrocytes exhibit diverse phenotypes in a region‐specific manner in brain and interact with β‐amyloid, tau, and α‐synuclein species as well as with microglia and neuronal circuits.

Activated astrocytes are likely to influence the trajectory of disease progression of neurodegenerative diseases, as determined by the stage of disease, individual susceptibility, and state of astroglial priming.

Modulation of astroglial activation may be a therapeutic strategy at various stages in the trajectory of neurodegenerative diseases to modify the disease course.