bluuebunny/crossref_metadata_2025 huggingface dataset:
Worse outcomes linked to ethnicity for early inflammatory arthritis in England and Wales: a national cohort study
Authors: Adas Maryam A , Norton Sam , Balachandran Sathiyaa , Alveyn Edward , Russell Mark D , Esterine Thomas , Amlani-Hatcher Paul , Oyebanjo Sarah , Lempp Heidi , Ledingham Joanna , Kumar Kanta , Galloway James B , Dubey Shirish
Published: May 2022

Objective

To assess variability in care quality and treatment outcomes across ethnicities in early inflammatory arthritis (EIA).

Methods

We conducted an observational cohort study in England and Wales from May 2018 to March 2020, including patients with a suspected/confirmed EIA diagnosis. Care quality was assessed against six metrics defined by national guidelines. Clinical outcomes were measured using DAS28. Outcomes between ethnic groups (‘White’, ‘Black’, ‘Asian’, ‘Mixed’, ‘Other’) were compared, and adjusted for confounders.

Results

A total of 35 807 eligible patients were analysed. Of those, 30 643 (85.6%) were White and 5164 (14.6%) were from ethnic minorities: 1035 (2.8%) Black; 2617 (7.3%) Asian; 238 (0.6%) Mixed; 1274 (3.5%) Other. In total, 12 955 patients had confirmed EIA, of whom 11 315 were White and 1640 were from ethnic minorities: 314 (2.4%) Black; 927 (7.1%) Asian; 70 (0.5%) Mixed; 329 (2.5%) Other. A total of 14 803 patients were assessed by rheumatology within three weeks, and 5642 started treatment within six weeks of referral. There were no significant differences by ethnicity. Ethnic minority patients had lower odds of disease remission at three months [adjusted odds ratio 0.79 (95% CI: 0.65, 0.96)] relative to White patients. Ethnic minorities were significantly less likely to receive initial treatment withMTX[0.68 (0.52, 0.90)] or with glucocorticoids [0.63 (0.49, 0.80)].

Conclusion

We demonstrate that some ethnic minorities are less likely to achieve disease remission in three months following EIA diagnosis. This is not explained by delays in referral or time to treatment. Our data highlight the need for investigation into the possible drivers of these inequitable outcomes and reappraisal of EIA management pathways.
Isorhamnetin: a flavonoid, attenuated doxorubicin-induced testicular injury via regulation of steroidogenic enzymes and apoptotic signaling gene expression in male rats
Authors: Mustafa Shama , Ijaz Muhammad Umar , ul Ain Qurat , Afsar Tayyaba , Almajwal Ali , Shafique Huma , Razak Suhail
Published: May 2022

Background

Male reproductive damage is one of the most adverse side effects of doxorubicin (DOX). Isorhamnetin is a natural flavonoid, which displays remarkable antioxidant potential.

Objective

The current research was designed to assess the protective effects of Isorhamnetin against DOX-instigated testicular damages.

Methods

Adult male Wistar rats (n=32) were divided into 4 groups: control, DOX (3 mg/kg i.p. 3 doses each after 1 week), DOX + Isorhamnetin (3 mg/kg 3 doses each after 1 week +10 mg/kg i.p. daily for 28 days, respectively), and Isorhamnetin (10 mg/kg i.p. per day). After 28 days of treatment, biochemical, spermatogenic, steroidogenic, hormonal, proapoptotic, antiapoptotic, and histopathological parameters were estimated.

Results

DOX exposure significantly decreased the activity of acid phosphatase, lactate dehydrogenase, and gamma-glutamyl transferase. Furthermore, DOX substantially decreased the activities of antioxidant enzymes, i.e. catalase, superoxide dismutase, glutathione reductase, and glutathione peroxidase along with protein content, whereas it increased the malondialdehyde level. It also reduced sperm progressive motility, viability, the number of hypoosmotic tail swelled spermatozoa, and epididymis sperm count and increased the sperm morphological anomalies (head, midpiece, and tail). Besides, it decreased the levels of follicle-stimulating hormone, luteinizing hormone, and plasma testosterone and lowered the expression of steroidogenic enzymes (3β-hydroxysteroid dehydrogenase, 17β-hydroxysteroid dehydrogenase, and steroidogenic acute regulatory protein) and testicular antiapoptotic marker (B-cell lymphoma 2) but increased the expression of proapoptotic markers (BCL2-associated X protein and caspase-3) along with histopathological impairments. However, isorhamnetin prevented all the damages caused by DOX.

Conclusion

Conclusively, Isorhamnetin can be used as a powerful mitigating agent to avert DOX-induced testicular damages.
The Association Between Sexual Orientation, BMI, Obesity Diagnosis, and Provider Recommendation for Weight Management
Authors: Wolfgang Kristen M. , Takeshita Junko , Fitzsimmons Robert , Guerra Carmen E.
Published: May 2022

(Abstracted from BMC Womens Health 2022;22(1):19)

Previous studies indicate that lesbian and bisexual (LB) females are more likely to be obese than straight females. Little is known, however, about whether provider diagnosis and recommendation for weight management vary across these populations.
Evaluation of Changes in Grams of Sugar Sold After the Implementation of the Seattle Sweetened Beverage Tax
Authors: Powell Lisa M. , Leider Julien , Oddo Vanessa M.
Published: May 2022

(Abstracted from JAMA Network Open 2021;4(11):e2132271)

Despite the robust association between added sugars, including those from sugar-sweetened beverages (SSBs) and obesity, type 2 diabetes, cardiovascular disease, and poor dental health, more than 50% of adults and 65% of children exceed recommended intake. Reducing consumption of added sugars is a key goal for Healthy People 2030, and taxation of SSBs is increasingly being used to accomplish this.
Evaluation of the Virtual Interview Format for Resident Recruitment as a Result of COVID-19 Restrictions: Residency Program Directors’ Perspectives
Authors: Ponterio Jane M. , Levy Lior , Lakhi Nisha A.
Published: May 2022

Purpose

Due to the COVID-19 pandemic, residency programs could not conduct in-person interviews during the 2020–2021 Match cycle and were forced to implement a virtual format. The authors conducted a nationwide survey of residency program directors (PDs) to assess their confidence in using a virtual platform to holistically evaluate applicants during the 2020–2021 Match cycle and their desire to continue virtual recruitment during forthcoming interview seasons.

Method

This prospective study was conducted by email questionnaire administered through the survey tool Survey Monkey to residency PDs from March 7, 2021–March 27, 2021. The residency PDs surveyed represented these subspecialties: internal medicine, general surgery, obstetrics and gynecology, pediatrics, psychiatry, and other. Email addresses of PDs were collected from a public list developed by the Accreditation Council for Graduate Medical Education. Surveys contained demographic questions, 4-point Likert scale questions evaluating several factors regarding the interview and matching process, and free-response questions.

Results

A total of 463 surveys were sent; response rate was 402 /463 (86.8%). Most PDs were less confident assessing an applicant’s interpersonal skills (247, 61.4%) and professionalism (239, 59.5%) using a virtual platform. Assessment of an applicant’s “fit” into the program was also challenging: 44.3% (178) of those surveyed disagreed with the statement that they could do so confidently. Additionally, 73.9% (297) of PDs found it challenging to gauge an applicant’s genuine interest and only 41.3% (166) strongly agreed or agreed that they could accurately represent their own program using a virtual platform. More than half of PDs (220, 54. 7%) found it more difficult to rank interviewees compared with previous in-person Match cycles.

Conclusions

Most residency PDs found virtual interviews convenient. However, difficulties in assessing fit virtually, gauging applicants’ interest, and showcasing their respective programs were challenges that may persist should virtual interviews continue post-pandemic.
Surgeons’ Perspective of Decision Making in Recurrent Diverticulitis
Authors: Hawkins Alexander T. , Rothman Russell L. , Geiger Timothy M. , Bonnet Kemberlee R. , Mutch Matthew G. , Regenbogen Scott E. , Schlundt David G. , Penson David F.
Published: May 2022

Objective:

This study employs qualitative methodology to assess surgeons’ perspective on decision making in management of recurrent diverticulitis to improve patient-centered decision making.

Background:

The decision to pursue colectomy for patients with recurrent diverticulitis is nuanced. Strategies to enact broad acceptance of guidelines for surgery are hindered because of a knowledge gap in understanding surgeons’ current attitudes and opinions.

Methods:

We performed semistructured interviews with board-certified North American general and colorectal surgeons who manage recurrent diverticulitis. We purposely sampled specialists by both surgeon and practice factors. An iterative inductive/deductive strategy was used to code and analyze the interviews and create a conceptual framework.

Results:

Twenty-five surgeons were enrolled over a 9-month period. There was diversity in surgeons’ gender, age, experience, training, specialty (colorectal vs general surgery), and geography. Surgeons described the difficult process to determine who receives an operation. We identified 7 major themes as well as 20 subthemes of the decision-making process. These were organized into a conceptual model. Across the spectrum of interviews, it was notable that there was a move over time from decisions based on counting episodes of diverticulitis to a focus on improving quality of life. Surgeons also felt that quality of life was more dependent on psychosocial factors than the degree of physiological dysfunction.

Conclusions:

Surgeons mostly have discarded older dogma in recommending colectomy for recurrent diverticulitis based on number and severity of episodes. Instead, decision making in recurrent diverticulitis is complex, involving multiple surgeon and patient factors and evolving over time. Surgeons struggle with this decision and education- or communication-based interventions that focus on shared decision-making warrant development.
How Are the Sleep Problems of Children in the US Foster Care System Addressed?
Authors: Alfano Candice A. , Valentine Madeline , Nogales Josefina Muñoz , Kim Jinu , Kim Josephine S. , Rigos Priscilla , McGlinchey Eleanor L. , Ripple Carol H. , Wolfson Amy R.
Published: May 2022

Objective:

Evidence of poor sleep health among children in foster care continues to mount, but information about whether and how sleep problems are addressed is unavailable. The goal of this study was to begin to fill these significant knowledge gaps.

Methods:

Four hundred eighty-five foster caregivers from across the United States completed a survey focused on the sleep health of one child, 4 to 11 years (M = 6.4; SD = 2.2) currently in their care. Caregivers provided quantitative and qualitative responses to questions regarding training, information, and services received in relation to their child's sleep. Caregivers also reported on the factors and strategies they perceived as most important for helping children in their care sleep well.

Results:

Only 13% of caregivers reported receiving any information/education about sleep from agencies or case workers, whereas 55% had sought help from a health provider related to their child's sleep. Nearly half of all caregivers (46%) reported giving their child melatonin. Caregivers reported that a bedtime routine/consistency, reassurance of safety/love, and a calming environment were most important for helping their child sleep well. A recurrent theme in qualitative responses was a need to mitigate child fear/anxiety at night.

Conclusion:

Children in foster care face a range of risk factors that increase the likelihood of poor/insufficient sleep, but these findings suggest this critical aspect of health requires greater clinical and research attention. As these data were collected during the initial months of the COVID-19 pandemic, replication studies are necessary.
Clinical variables accompanying salt-sensitive essential hypertension in ethnic Kashmiri population
Authors: Chachoo Javaid , Mushtaq Nausheen , Jan Sami , Majid Sabhiya , Mohammad Iqbal
Published: May 2022

Background:

Salt sensitivity is actually a measure of an individual's blood pressure response to salt intake. It has been reported that people who are salt sensitive have high prevalence of hypertension and target organ damage. The link between dietary salt intake and hypertension is well established, and a reduction in salt intake has been shown to lower blood pressure.

Scope:

In Kashmir, this achieves significance because of a high incidence of hypertension along with a high salt intake among ethnic Kashmiris.

Design and methods:

We analysed clinical variables accompanying salt sensitive hypertension among Kashmiri population in our on-going salt sensitivity study on 770 Kashmiri patients (250 men, 520 women) of age group 18years and above from March 2020 to June 2021. We studied the clinical variables accompanying salt sensitivity and the difference in their blood pressure on. a low salt diet (mean = 2 g/day) vs. their usual salt intake (mean = 11 g/day). To document compliance of salt-restricted diet, we used 24-h urinary NaCl estimation as a surrogate marker for salt intake estimation.

Results:

We observed, a huge drop in SBP (−28.9 mmHg), DBP (−17.6 mmHg) and mean arterial pressure (−21.3mmHg) in this cohort of 770 ethnic Kashmiris on a strict salt restricted diet. And that women, urban inhabitants, and nonsmokers are more prone to the risk of developing salt sensitive hypertension. Physical activity had no effect on salt sensitivity.

Conclusion:

As per our study, salt restriction has a major role in treatment of Hypertension in Kashmiri Population. More studies need to be focused on this vital area.
The correlation between VitD3 levels and the disease activity of childhood-onset systemic lupus erythematosus
Authors: Cheng Kan-Hung , Tsai Ming-Chin , Fu Lin-Shien
Published: May 2022

Background:

There is growing evidence linking low levels of vitamin D3 to an increased risk of many autoimmune diseases. Compared to the general population, hypovitaminosis D is more prevalent among children with systemic lupus erythematosus (SLE), which can be associated with sun exposure avoidance, long-term corticosteroid treatment, and renal disease. Therefore, we launched this study to assess the correlation between 25 (OH) D3 (VitD3) levels and the disease activity of children with SLE (cSLE) in Taiwan.

Methods:

From September to December 2018, we recruited 31 cSLE patients from the Pediatric Out-patient Department of Taichung Veterans General Hospital. Their basic data, including SLE disease index 2000 (SLEDAI-2K) score, laboratory values, prescribed drugs and VitD3 levels were collected and analyzed statistically.

Results:

The mean serum VitD3 concentration was 19.7 ± 7.9 ng/mL and SLEDAI-2K 6.2 ± 5.0. Those patients (N = 16) with an SLEDAI-2K≦4 had higher VitD3 levels when compared to those (N = 15) with an SLEDAI-2K>4 (22.9 ± 7.7 vs 16.3 ± 6.7 points, p = 0.020). Five patients not taking systemic corticosteroids (SCS) had significantly higher VitD3 levels and lower SLEDAI-2K than those who took SCS (N = 26). Additionally, we found VitD3 levels to be negatively correlated to SLEDAI-2K (rs = −0.55, p = 0.001) and daily SCS dosages (rs = −0.49, p = 0.005).

Conclusion:

This study shows that VitD3 deficiency is common in patients with cSLE. It was also noted that serum VitD3 levels negatively correlate to SLEDAI-2K, which can be partially explained by less usage of SCS.
Dynamic changes in signal-averaged P wave after catheter ablation of atrial fibrillation
Authors: Yugo Dony , Kuo Ming-Jen , Hu Yu-Feng , Liu Chih-Min , Lin Yenn-Jiang , Chang Shih-Lin , Lo Li-Wei , Chao Tze-Fan , Chung Fa-Po , Liao Jo-Nan , Chang Ting-Yung , Lin Chin-Yu , Tuan Ta-Chuan , Kuo Ling , Liu Shin-Huei , Ton An Nu- Khanh , Chhay Chheng , Elimam Ahmed , Chen Shih-Ann
Published: May 2022

Background:

The comprehensive surveillance for interval changes in signal-averaged P-wave (SAPW) after pulmonary vein isolation (PVI) remains lacking. We aimed to analyze the SAPW parameters before and after PVI and explored their link to the left atrial electrical properties.

Methods:

Eighteen patients with paroxysmal atrial fibrillation receiving primary catheter ablation were enrolled. SAPW parameters, including root mean square voltages in the last 40, 30, and 20 ms (RMS40, RMS30, and RMS20, respectively), the total P-wave (RMSt), the integral of P-wave potentials (Int-p), and P-wave duration (fPWD), were measured before and after PVI and correlated to the left atrial activation time (LAT) and mean left atrial voltage (LAV) from electro-anatomical mapping.

Results:

Compared with the SAPW before PVI, fPWD (before vs after PVI: 144.1 ± 5.2 vs 135.1 ± 11.9 ms, p = 0.02), Int-p (687.4 ± 173.1 vs 559 ± 202.5 mVms, p = 0.01), and RMSt (6.44 ± 1.3 vs 5.44 ± 2.0 mV, p = 0.04) all decreased after PVI. RMS20, RMS30, and RMS40 showed no significant difference. Similarly, LAT (97.5 ± 9.3 vs 90.5 ± 9.3 ms, p = 0.008) and LAV (1.37 ± 0.27 vs 0.96 ± 0.31 mV, p = 0.001) decreased after PVI. Although consistent changes after PVI were observed between SAPW parameters and LAT or LAV, no linear correlation was observed among them.

Conclusion:

The consistent changes in SAPW and left atrial electrical properties after PVI suggest that SAPW may be used as a noninvasive tool to monitor the responses to PVI.
Comparison of prognoses between cirrhotic and noncirrhotic patients with hepatocellular carcinoma and esophageal varices undergoing surgical resection
Authors: Chen Yu-Jen , Su Chien-Wei , Wei Cheng-Yi , Chau Gar-Yang , Chen Ping-Hsien , Chao Yee , Huang Yi-Hsiang , Wu Jaw-Ching , Yang Tsung-Chieh , Lee Pei-Chang , Hou Ming-Chih
Published: May 2022

Background:

Esophageal varices (EV) is common and is a poor prognostic factor for patients with hepatocellular carcinoma (HCC). However, the outcomes between cirrhotic and noncirrhotic HCC patients with EV is not well studied. The present study aimed to investigate the clinical manifestations and prognoses of HCC patients after surgical resection stratified by the cirrhosis status.

Methods:

A total of 111 patients with HCC and EV, who underwent surgical resection, were retrospectively enrolled between July 2003 and July 2019. The diagnosis of liver cirrhosis was established using the Ishak fibrosis score F5 or F6 in the nontumor part of liver specimens. Prognostic factors were analyzed using the Cox proportional hazards model.

Results:

There were 85 (76.6%) and 26 (23.4%) patients with and without cirrhosis, respectively. Compared with those without cirrhosis, there were more females, less seropositive rate of hepatitis B surface antigen (HBsAg), more seropositive rate of antibody against to hepatitis C virus (HCV), less albumin-bilirubin (ALBI) grade 1, lower platelet count, and more had tumor burden within the Milan criteria in cirrhotic patients. Cirrhotic patients had a higher risk of posthepatectomy decompensation compared to noncirrhotic patients (hazard ratio 9.577, p = 0.017). No difference was observed in overall survival and recurrence-free survival between patients with or without cirrhosis.

Conclusion:

Compared with patients without cirrhosis, cirrhotic patients with HCC and EV are vulnerable to posthepatectomy decompensation. However, cirrhosis is not a poor prognostic factor of overall survival and recurrence for HCC patients after surgical resection.
Factors Related to Patients' Self-care and Self-care Confidence in Korean Patients With Heart Failure and Their Caregivers
Authors: Heo Seongkum , Shin Mi-Seung , Lee Mee Ok , Kim Sangsuk , Kim Sun Hwa , Randolph Justus , Jun Se-Ran , An Minjeong , Ounpraseuth Songthip , Kim JinShil
Published: May 2022

Background

The relationships of patient factors and caregiver contribution to patients' self-care to different types of self-care have been rarely examined in Korean patients with heart failure.

Objective

The aim of this study was to examine patient (ie, age, depressive symptoms, and self-care confidence) and caregiver (ie, caregiver contribution to self-care maintenance and self-care management, and caregiver confidence in contributing to self-care) factors related to different types of self-care (ie, self-care maintenance, symptom perception, and self-care management) and self-care confidence in Korean patients with heart failure.

Methods

In this cross-sectional, correlational study, data from 41 pairs of patients (mean age, 68.0 years) and caregivers (mean age, 54.1 years) were collected and analyzed using multiple regression.

Results

Higher levels of self-care confidence in patients were related to higher levels of self-care maintenance in patients. Higher levels of self-care confidence in patients were related to higher levels of symptom perception. Higher levels of self-care confidence in patients and caregiver contribution to self-care maintenance were related to higher levels of self-care management. Less severe depressive symptoms in patients and higher levels of caregiver confidence in contributing to self-care were related to higher levels of self-care confidence.

Conclusion

Different patient and caregiver factors were related to different types of self-care and self-care confidence in Korean patients, but patients' self-care confidence was related to all types of self-care. Clinicians and researchers need to develop and deliver effective interventions to both patients and their caregivers to improve patients' self-care confidence and, in turn, self-care, considering different factors associated with each type of self-care.
Extracorporeal Membrane Oxygenation Circuits in Parallel for Refractory Hypoxemia in COVID-19: A Case Series
Authors: Patel Yatrik J. , Stokes John W. , Gannon Whitney D. , Francois Sean A. , Wu Wei Kelly , Rice Todd W. , Bacchetta Matthew
Published: May 2022

Refractory hypoxemia despite the use of extracorporeal membrane oxygenation (ECMO) for coronavirus disease 2019 (COVID-19)–related acute respiratory distress syndrome remains a challenging problem. A single ECMO circuit may not provide adequate physiologic support in the setting of an elevated cardiac output, physiologic demand, and impaired gas exchange. In select patients with refractory hypoxemia, addition of a second ECMO circuit in parallel can improve oxygenation, facilitate lung protective ventilation, awakening, and physical rehabilitation. We report the largest case series to date of patients receiving ECMO circuits in parallel and the first to report this approach in COVID-19.
Evaluation of the 18F-FDG-PET/CT uptake association with pathological and immunohistochemistry features in esophagogastric adenocarcinoma
Authors: Simionato Perrotta Fernando , Ribeiro Ulysses , Mester Marcelo , Sobroza de Mello Evandro , Sado Heitor Naoki , Bezerra Pinheiro Rafaela Brito , Tustumi Francisco , Buchpiguel Carlos Alberto , Zilberstein Bruno , Sallum Rubens Antonio Aissar , Ceconello Ivan
Published: May 2022

Background

The present study aimed to analyze the association between 18F-fluorodeoxyglucose (FDG) uptake and histologic panel in esophagogastric adenocarcinoma.

Methods

We retrospectively enrolled 26 patients with histologically confirmed esophageal, gastroesophageal junction and gastric adenocarcinoma that have been submitted to pretreatment FDG-PET/CT. We collected the cancer tissue sample of each patient and performed immunohistochemical analyses of the glucose transport protein 1 (GLUT-1), Ki-67, cysteine aspartate-specific proteinases (Caspase)-3 and hexokinase-1, and evaluated the association of these parameters with FDG uptake. The FDG uptake was measured by tumor standardized uptake value (SUV), metabolic tumor volume (MTV), and Total Lesion Glycolysis (TLG). Besides, we analyzed the association of FDG uptake and tumor location, Lauren’s histologic subtype, grade of cellular differentiation and intratumoral inflammatory infiltrate.

Results

We found a positive association between GLUT-1 with SUV and TLG, Caspase-3 and SUV and inflammation grade with SUV.

Conclusion

Tumor inflammation infiltrate, GLUT-1 and Caspase-3 correlated with 18F-FDG uptake in PET/CT in esophagogastric adenocarcinoma. These findings may help understand the pathologic PET/CT significance in cancer. Understanding the meaning of the 18F-FDG uptake in the field of tumor histologic and immunohistochemistry features is essential to allow the evolution of PET/CT application in esophageal and gastric carcinomas.
The effect of coronavirus disease 2019 pneumonia on myocardial ischemia detected by single-photon emission computed tomography myocardial perfusion imaging
Authors: Bilge Önder , Kömek Halil , Kepenek Ferat , Taştan Ercan , Gündoğan Cihan , Tatli İsmail , Öztürk Cansu , Akin Halil , Işik Ferhat , Kavak Şeyhmus , Aslan Burhan , Akyüz Abdurrahman , Kanbal Çap Neşe , Erdoğan Emrah
Published: May 2022

Objective

We aimed to examine the effects of COVID-19 pneumonia on cardiac ischemia detected by myocardial perfusion imaging with single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in patients presenting with chest pain and shortness of breath after recovery from COVID-19.

Materials and method

Patients with a history of COVID-19 confirmed by reverse transcriptase-PCR test who underwent SPECT-MPI for the evaluation of ischemia with the complaints of chest pain and shortness of breath were screened for this study. Patients who underwent thorax CT during the acute period of the COVID-19 were included. Patients with and without pneumonia were determined based on computed tomographic criteria. The patients with a summed stress score of at least 4 on SPECT-MPI were considered to have abnormal MPI in terms of ischemia.

Results

A total of 266 patients were included in the study. Sixty-five (24%) patients had ischemia findings on SPECT-MPI. Thorax CT showed pneumonia in 152 (57%) patients, and the patients were divided into two groups as pneumonia and nonpneumonia. Abnormal SPECT-MPI scores, which represented myocardial ischemia, were higher in the pneumonia group. Multivariate logistic regression analyses showed that the presence of hyperlipidemia and pneumonia on CT increased the risk of ischemia on SPECT-MPI (OR, 2.08; 95% CI, 1.08–3.99; P-value = 0.029; and OR, 2.90; 95% Cl, 1.52–5.54; P-value = 0.001, respectively).

Conclusion

COVID-19 pneumonia was identified as an independent predictor of ischemia on SPECT-MPI. Symptoms including chest pain and shortness of breath in patients who have had COVID-19 pneumonia may be attributed to coronary ischemia.
Favorable tumor uptake and nuclear transport of Auger electrons by nuclear targeting with 111In-trastuzumab in an intraperitoneal tumor mouse model
Authors: Keiko Li Huizi , Hasegawa Sumitaka
Published: May 2022

Objectives

The 111In-labeled anti-HER2 antibody trastuzumab modified with a nuclear-localizing sequence (NLS) peptide (111In-trastuzumab-NLS) is a radiopharmaceutical candidate for Auger electron radioimmunotherapy (AE-RIT). However, in-vivo action of 111In-trastuzumab-NLS is poorly understood in intraperitoneal tumors. We aimed to elucidate the nuclear targeting activity of 111In-trastuzumab-NLS in a mouse model of intraperitoneal tumors.

Methods

Trastuzumab, trastuzumab-NLS-S with shorter NLS peptides, and trastuzumab-NLS-L with longer NLS peptides were tested in an intraperitoneal tumor xenograft. The AE-emitting radionuclide 111In was labeled with these antibodies. The cell-binding activity, nuclear importation, and cytotoxicity of those radiolabeled antibodies were examined in human cancer cell lines. Analyses of the biodistribution and in-vivo nuclear importation of 111In were conducted in a mouse model.

Results

The two111In-trastuzumab-NLS variants delivered the radionuclide into the nucleus more efficiently and had a comparable cytotoxicity to 111In-trastuzumab against human gastric cancer cells, although had a lower cell binding affinity. 111In-trastuzumab-NLS-L exhibited both a superior tumor uptake and in vivo nuclear transportation of the radionuclide than 111In-trastuzumab.

Conclusion

Nuclear targeting using 111In-trastuzumab-NLS promotes a more efficient tumor cell uptake and subsequent nuclear translocation of the 111In AE-emitting radionuclide in vivo. This radio-immunoconjugate will likely be an effective agent for HER2-targeting by AE-RIT.
The role of volumetric and textural analysis of pretreatment 18F-fluorodeoxyglucose PET/computerized tomography images in predicting complete response to transarterial radioembolization in hepatocellular cancer
Authors: Karahan Şen Nazli Pinar , Alataş Özkan , Gülcü Aytaç , Özdoğan Özhan , Derebek Erkan , Çapa Kaya Gamze
Published: May 2022

Objective

This study evaluates the role of pretreatment 18F-FDG PET/CT in predicting the response to treatment in patients with hepatocellular cancer (HCC) who applied transarterial radioembolization (TARE) via the volumetric and texture features extracted from 18F-FDG PET/CT images.

Methods

Thirty-three patients with HCC who had applied TARE [lobar (LT) or superselective (ST)] after 18F-FDG PET/CT were included in the study. Response to the treatment was evaluated from posttherapy magnetic resonance (MR). Patients were divided into two groups: the responder group (RG) (complete responders) and non-RG (NRG) (including partial response, stabile, and progressive). Metabolic tumor volume (MTV) and total lesion glycolysis (TLG) and texture features were extracted from PET/CT images. The differences among MTV, TLG, and texture features between response groups were analyzed with the Mann–Whitney U test. ROC analysis was performed for features with P < 0.05. Spearman correlation analysis was used, and features with correlation coefficient < 0.8 were evaluated with the logistic regression analysis.

Results

Significant differences were detected in TLG, MTV, SHAPE_compacity, GLCM_correlation, GLRLM_GLNU, GLRLM_RLNU, NGLDM_coarseness, NGLDM_busyness, GLZLM_LZHGE, GLZLM_GLNU, and GLZLM_ZLNU between RG and NRG. Multivariate analysis demonstrated that MTV was the only meaningful parameter with an AUC of 0.827 (P = 0.002; 95% CI, 0.688–0.966). The best cutoff value was determined as 74.11 ml with 78.9% sensitivity and 78.6% specificity in discriminating nonresponders.

Conclusion

In predicting the curative effect of TARE, multivariate analysis results demonstrated that MTV was the only independent predictor, and MTV higher than 74.11 ml were determined the best predictor of nonresponders.
PET/CT features of a novel gallium-68 labelled hypoxia seeking agent in patients diagnosed with tuberculosis: a proof-of-concept study
Authors: Bresser Philippa L. , Sathekge Mike M. , Vorster Mariza
Published: May 2022

Introduction

Positron emission tomography/computed tomography (PET/CT) in infection and inflammation has yielded promising results across a range of radiopharmaceuticals. In particular, PET/CT imaging of tuberculosis (TB) allows for a better understanding of this complex disease by providing insights into molecular processes within the TB microenvironment. TB lesions are hypoxic with research primarily focussed on cellular processes occurring under hypoxic stress. With the development of hypoxia seeking PET/CT radiopharmaceuticals, that can be labelled in-house using a germanium-68/gallium-68 (68Ge/68Ga) generator, a proof-of-concept for imaging hypoxia in TB is presented.

Methods

Ten patients diagnosed with TB underwent whole-body PET/CT imaging, 60–90 min after intravenous administration of 74–185 MBq (2–5 mCi) 68Ga-nitroimidazole. No oral or intravenous contrast was administered. Images were visually and semiquantitatively assessed for abnormal 68Ga-uptake in the lungs.

Results

A total of 28 lesions demonstrating hypoxic uptake were identified. Low- to moderate-uptake was seen in nodules, areas of consolidation and cavitation as well as effusions. The mean standard uptake value (SUVmean) of the lesions was 0.47 (IQR, 0.32–0.82) and SUVmax was 0.71 (IQR, 0.41–1.11). The lesion to muscle ratio (median, 1.70; IQR, 1.15–2.31) was higher than both the left ventricular and the aorta lesion to blood ratios.

Conclusion

Moving towards the development of unique host-directed therapies (HDT), modulation of oxygen levels may improve therapeutic outcome by reprogramming TB lesions to overcome hypoxia. This proof-of-concept study suggests that hypoxia in TB lesions can be imaged and quantified using 68Ga-nitroimidazole PET/CT. Subsequently, hypoxic load can be estimated to inform personalised treatment plans of patients diagnosed with TB.
Lenvatinib Plus Pembrolizumab for Advanced Endometrial Cancer
Authors: Makker Vicky , Colombo Nicoletta , Herráez Antonio Casado , Santin Alessandro D. , Colomba Emeline , Miller David S. , Fujiwara Keiichi , Pignata Sandro , Baron-Hay Sally , Ray-Coquard Isabelle , Shapira-Frommer Ronnie , Ushijima Kimio , Sakata Jun , Yonemori Kan , Kim Yong Man , Guerra Eva M. , Sanli Ulus A. , McCormack Mary M. , Smith Alan D. , Keefe Stephen , Bird Steven , Dutta Lea , Orlowski Robert J. , Lorusso Domenica
Published: May 2022

(Abstracted from N Engl J Med 2022;386:437–448)

Little consensus exists on optimal treatment for advanced or recurrent endometrial cancer after disease progression with platinum-based chemotherapy. Lenvatinib is a multitargeted tyrosine kinase inhibitor that as a single agent has demonstrated limited efficacy as second-line treatment of recurrent endometrial carcinoma.
Mechanism of Spindle Pole Organization and Instability in Human Oocytes
Authors: So Chun , Menelaou Katerina , Uraji Julia , Harasimov Katarina , Steyer Anna M. , Seres K. Bianka , Bucevičius Jonas , Lukinavičius Gražvydas , Möbius Wiebke , Sibold Claus , Tandler-Schneider Andreas , Eckel Heike , Moltrecht Rüdiger , Blayney Martyn , Elder Kay , Schuh Melina
Published: May 2022

(Abstracted from Science 2022;375:eabj3944)

Approximately 25% to 50% of human eggs are aneuploid, with even higher rates among older women. Aneuploidy is a leading cause of abnormal embryonic development resulting in miscarriage and genetic disorders.
Impact of a 1-Year Pediatric Emergency Medicine Training Program for International Medical Graduates
Authors: Cardenas Sandra , Scolnik Dennis , Jarvis D. Anna , Thull-Freedman Jennifer
Published: May 2022

Objectives

The Hospital for Sick Children in Toronto has offered a 1-year subspecialty residency training program in pediatric emergency medicine (PEM) to Canadian and internationally trained pediatricians and emergency physicians since 1993. The program is intended to support clinical service delivery while simultaneously offering a unique educational opportunity to Canadian and international physicians who desire 1 year of clinically focused training. We describe the experiences and career outcomes of participants who completed this program.

Methods

Two surveys were sent to the 68 individuals who completed the clinical fellowship program from its inception in 1993 until 2014. A blinded survey focused on the fellowship experience and subsequent career activities. A nonblinded survey subsequently determined whether participants had served as a medical director or training program director.

Results

Sixty of the 68 participants (88%) completed the blinded survey. Ninety-one percent were in practice in emergency medicine. Twenty-five percent of the participants were living in Canada, compared with 17% before completing the program. This net migration of 8% was not significant (P = 0.26). Thirty-six of the 50 participants (72%) who applied from outside Canada responded to the nonanonymous survey; 18 (50%) had served as an emergency department medical director, and 18 (50%) reported serving as a PEM training program director.

Conclusions

Many participants attained leadership positions in PEM in countries outside of North America and/or participated in training program development. There was no significant change in the proportion of participants living in North America at the time of application compared with the time of survey completion.
A conceptual framework to integrate cold-survival strategies: torpor, resistance and seasonal migration
Authors: Auteri Giorgia G.
Published: May 2022

Freezing temperatures are inherently challenging for life, which is water based. How species cope with these conditions fundamentally shapes ecological and evolutionary processes. Despite this, there is no comprehensive conceptual framework for cold-survival strategies—seasonal migration, cold resistance and torpor. Here, I propose a framework with four components for conceptualizing and quantifying cold-survival strategies. Cold-survival strategies are (i) collectively encompassed by the proposed framework, and that this full breadth of strategies should be considered in focal species or systems (
comprehensive consideration
). These strategies also (ii) exist on a spectrum, such that species can exhibit
partial use
of strategies, (iii) are non-exclusive, such that some species use multiple strategies concurrently (
combined use
) and (iv) should collectively vary inversely and proportionally with one another when controlling for the external environment (e.g. when considering species that occur in sympatry in their summer range), such that use of one strategy reduces, collectively, the use of others (
proportional use
). This framework is relevant to understanding fundamental patterns and processes in evolution, ecology, physiology and conservation biology.
Understanding the role of wild ruminants in anthelmintic resistance in livestock
Authors: Brown Tony L. , Airs Paul M. , Porter Siobhán , Caplat Paul , Morgan Eric R.
Published: May 2022

Wild ruminants are susceptible to infection from generalist helminth species, which can also infect domestic ruminants. A better understanding is required of the conditions under which wild ruminants can act as a source of helminths (including anthelmintic-resistant genotypes) for domestic ruminants, and vice versa, with the added possibility that wildlife could act as
refugia
for drug-susceptible genotypes and hence buffer the spread and development of resistance. Helminth infections cause significant productivity losses in domestic ruminants and a growing resistance to all classes of anthelmintic drug escalates concerns around helminth infection in the livestock industry. Previous research demonstrates that drug-resistant strains of the pathogenic nematode
Haemonchus contortus
can be transmitted between wild and domestic ruminants, and that gastro-intestinal nematode infections are more intense in wild ruminants within areas of high livestock density. In this article, the factors likely to influence the role of wild ruminants in helminth infections and anthelmintic resistance in livestock are considered, including host population movement across heterogeneous landscapes, and the effects of climate and environment on parasite dynamics. Methods of predicting and validating suspected drivers of helminth transmission in this context are considered based on advances in predictive modelling and molecular tools.
Face masking and COVID-19: potential effects of variolation on transmission dynamics
Authors: Levine Zachary , Earn David J. D.
Published: May 2022

Face masks do not completely prevent transmission of respiratory infections, but masked individuals are likely to inhale fewer infectious particles. If smaller infectious doses tend to yield milder infections, yet ultimately induce similar levels of immunity, then masking could reduce the prevalence of severe disease even if the total number of infections is unaffected. It has been suggested that this effect of masking is analogous to the pre-vaccination practice of variolation for smallpox, whereby susceptible individuals were intentionally infected with small doses of live virus (and often acquired immunity without severe disease). We present a simple epidemiological model in which mask-induced variolation causes milder infections, potentially with lower transmission rate and/or different duration. We derive relationships between the effectiveness of mask-induced variolation and important epidemiological metrics (the basic reproduction number and initial epidemic growth rate, and the peak prevalence, attack rate and equilibrium prevalence of severe infections). We illustrate our results using parameter estimates for the original SARS-CoV-2 wild-type virus, as well as the Alpha, Delta and Omicron variants. Our results suggest that if variolation is a genuine side-effect of masking, then the importance of face masks as a tool for reducing healthcare burdens from COVID-19 may be under-appreciated.
Secondary cell wall patterning—connecting the dots, pits and helices
Authors: Xu Huizhen , Giannetti Alessandro , Sugiyama Yuki , Zheng Wenna , Schneider René , Watanabe Yoichiro , Oda Yoshihisa , Persson Staffan
Published: May 2022

All plant cells are encased in primary cell walls that determine plant morphology, but also protect the cells against the environment. Certain cells also produce a secondary wall that supports mechanically demanding processes, such as maintaining plant body stature and water transport inside plants. Both these walls are primarily composed of polysaccharides that are arranged in certain patterns to support cell functions. A key requisite for patterned cell walls is the arrangement of cortical microtubules that may direct the delivery of wall polymers and/or cell wall producing enzymes to certain plasma membrane locations. Microtubules also steer the synthesis of cellulose—the load-bearing structure in cell walls—at the plasma membrane. The organization and behaviour of the microtubule array are thus of fundamental importance to cell wall patterns. These aspects are controlled by the coordinated effort of small GTPases that probably coordinate a Turing's reaction–diffusion mechanism to drive microtubule patterns. Here, we give an overview on how wall patterns form in the water-transporting xylem vessels of plants. We discuss systems that have been used to dissect mechanisms that underpin the xylem wall patterns, emphasizing the VND6 and VND7 inducible systems, and outline challenges that lay ahead in this field.
Tracking sexual dimorphism of facial width-to-height ratio across the lifespan: implications for perceived aggressiveness
Authors: Summersby Stephanie , Harris Bonnie , Denson Thomas F. , White David
Published: May 2022

The facial width-to-height ratio (FWHR) influences social judgements like perceived aggression. This may be because FWHR is a sexually dimorphic feature, with males having higher FWHR than females. However, evidence for sexual dimorphism is mixed, little is known about how it varies with age, and the relationship between sexual dimorphism and perceived aggressiveness is unclear. We addressed these gaps by measuring FWHR of 17 607 passport images of male and female faces across the lifespan. We found larger FWHR in males only in young adulthood, aligning with the stage most commonly associated with mate selection and intrasexual competition. However, the direction of dimorphism was reversed after 48 years of age, with females recording larger FWHRs than males. We then examined how natural variation in FWHR affected perceived aggressiveness. The relationship between FWHR and perceived aggressiveness was strongest for males at 27–33 and females at 34–61. Raters were most sensitive to differences in FWHR for young adult male faces, pointing to enhanced sensitivity to FWHR as a cue to aggressiveness. This may reflect a common mechanism for evaluating male aggressiveness from variability in structural (FWHR) and malleable (emotional expression) aspects of the face.
Flexible sutures reduce bending moments in shells: from the echinoid test to tessellated shell structures
Authors: Marmo Francesco , Perricone Valentina , Cutolo Arsenio , Daniela Candia Carnevali Maria , Langella Carla , Rosati Luciano
Published: May 2022

In the field of structural engineering, lightweight and resistant shell structures can be designed by efficiently integrating and optimizing form, structure and function to achieve the capability to sustain a variety of loading conditions with a reduced use of resources. Interestingly, a limitless variety of high-performance shell structures can be found in nature. Their study can lead to the acquisition of new functional solutions that can be employed to design innovative bioinspired constructions. In this framework, the present study aimed to illustrate the main results obtained in the mechanical analysis of the echinoid test in the common sea urchinParacentrotus lividus(Lamarck, 1816) and to employ its principles to design lightweight shell structures. For this purpose, visual survey, photogrammetry, three-dimensional modelling, three-point bending tests and finite-element modelling were used to interpret the mechanical behaviour of the tessellated structure that characterize the echinoid test. The results achieved demonstrated that this structural topology, consisting of rigid plates joined by flexible sutures, allows for a significant reduction of bending moments. This strategy was generalized and applied to design both free-form and form-found shell structures for architecture exhibiting improved structural efficiency.
Dynamic proteome allocation regulates the profile of interaction of auxotrophic bacterial consortia
Authors: Reyes-González D. , De Luna-Valenciano H. , Utrilla J. , Sieber M. , Peña-Miller R. , Fuentes-Hernández A.
Published: May 2022

Microbial ecosystems are composed of multiple species in constant metabolic exchange. A pervasive interaction in microbial communities is metabolic cross-feeding and occurs when the metabolic burden of producing costly metabolites is distributed between community members, in some cases for the benefit of all interacting partners. In particular, amino acid auxotrophies generate obligate metabolic inter-dependencies in mixed populations and have been shown to produce a dynamic profile of interaction that depends upon nutrient availability. However, identifying the key components that determine the pair-wise interaction profile remains a challenging problem, partly because metabolic exchange has consequences on multiple levels, from allocating proteomic resources at a cellular level to modulating the structure, function and stability of microbial communities. To evaluate how ppGpp-mediated resource allocation drives the population-level profile of interaction, here we postulate a multi-scale mathematical model that incorporates dynamics of proteome partition into a population dynamics model. We compare our computational results with experimental data obtained from co-cultures of auxotrophic
Escherichia coli
K12 strains under a range of amino acid concentrations and population structures. We conclude by arguing that the stringent response promotes cooperation by inhibiting the growth of fast-growing strains and promoting the synthesis of metabolites essential for other community members.
The effect of age and initial compression on the force relaxation response of the femur in elderly women
Authors: Martelli Saulo
Published: May 2022

The effect of force amount, age, body weight and bone mineral density (BMD) on the femur's force relaxation response was analysed for 12 donors (age: 56–91 years). BMD and fracture load,FL, were estimated from clinical CT images. The 30 min force relaxation was obtained using a constant compression generating an initial forceF0between 7% and 78% ofFL. The stretched decay function (F(t) =A×e(−t/τ)β) proposed earlier for bone tissue was fitted to the data and analysed using robust linear regression. The relaxation function fitted well to all the recordings (R2= 0.99). The relative initial force was bilinearly associated (R2= 0.83) to the shape factor,β, and the characteristic time,τ, whenF0/FLwas less than 0.4, althoughβwas no longer associated withF0/FLby pooling all the data. The characteristic timeτincreased with age (R2= 0.37,p= 0.03) explaining 35% of the variation ofτin the entire dataset. In conclusion, the relative initial force mostly determines the femur's force relaxation response, although the early relaxation response under subcritical loading is variable, possibly due to damage occurring at subcritical loading levels.