bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring use of coercion in the Norwegian ambulance service – a qualitative study
Authors: Thorvaldsen Nina Oeye , Husum Tonje Lossius , Sollid Stephen J.M.
Published: September 2023

Background

Healthcare laws allow for exceptions from the consent requirement when patients are not competent to consent or pose a danger to themselves or others. In these cases, the use of coercion may be an alternative to voluntary health care. Ambulance personnel are regularly confronted with patients who need healthcare but refuse it and/or refuse to cooperate. This study aimed to explore ambulance personnel`s experience with use of coercion and factors influencing the use of coercion in the ambulance service in Norway.

Method

We conducted two focus group interviews with a total of eight informants, all ambulance personnel from a large Norwegian ambulance service. Digital recordings of the interviews were transcribed verbatim and analysed using systematic text condensation.

Results

The informants` stories revealed several methods of coercion used by the ambulance personnel; physical coercion, pragmatic coercion, pharmacological coercion and coercion used to ensure the patient is secured during transportation. The main reasons for using coercion were preventing patients from harming themselves or others and to ensure that patients unable to consent receive healthcare considered necessary. Systemic factors as difficulty of applying the law to real-life situations, and organizational factors as fear of breaching guidelines, experienced lack of support from the management, fear of charges of misconduct, and lack of training in assessing patients´ competence to consent seem to influence ambulance personnels use of coercion.

Conclusion

Ethical grey areas in clinical practice emphasize the need for clinical discretion. Despite the fact that regulatory provisions allow for exceptions from the requirement to obtain consent, transferring these regulations to real life prehospital settings can be difficult. Consequently, the decisions made by ambulance personnel in clinical situations are highly influenced by organizational ethos and guidelines. The informants describe the coercive interventions they have employed to manage patients who are deemed to require healthcare but refuse it and/or refuse to cooperate.
Advanced respiratory mechanics assessment in mechanically ventilated obese and non-obese patients with or without acute respiratory distress syndrome
Authors: Beloncle François M. , Richard Jean-Christophe , Merdji Hamid , Desprez Christophe , Pavlovsky Bertrand , Yvin Elise , Piquilloud Lise , Olivier Pierre-Yves , Chean Dara , Studer Antoine , Courtais Antonin , Campfort Maëva , Rahmani Hassene , Lesimple Arnaud , Meziani Ferhat , Mercat Alain
Published: September 2023

Background

Respiratory mechanics is a key element to monitor mechanically ventilated patients and guide ventilator settings. Besides the usual basic assessments, some more complex explorations may allow to better characterize patients’ respiratory mechanics and individualize ventilation strategies. These advanced respiratory mechanics assessments including esophageal pressure measurements and complete airway closure detection may be particularly relevant in critically ill obese patients. This study aimed to comprehensively assess respiratory mechanics in obese and non-obese ICU patients with or without ARDS and evaluate the contribution of advanced respiratory mechanics assessments compared to basic assessments in these patients.

Methods

All intubated patients admitted in two ICUs for any cause were prospectively included. Gas exchange and respiratory mechanics including esophageal pressure and end-expiratory lung volume (EELV) measurements and low-flow insufflation to detect complete airway closure were assessed in standardized conditions (tidal volume of 6 mL kg−1 predicted body weight (PBW), positive end-expiratory pressure (PEEP) of 5 cmH2O) within 24 h after intubation.

Results

Among the 149 analyzed patients, 52 (34.9%) were obese and 90 (60.4%) had ARDS (65.4% and 57.8% of obese and non-obese patients, respectively, p = 0.385). A complete airway closure was found in 23.5% of the patients. It was more frequent in obese than in non-obese patients (40.4% vs 14.4%, p < 0.001) and in ARDS than in non-ARDS patients (30% vs. 13.6%, p = 0.029). Respiratory system and lung compliances and EELV/PBW were similarly decreased in obese patients without ARDS and obese or non-obese patients with ARDS. Chest wall compliance was not impacted by obesity or ARDS, but end-expiratory esophageal pressure was higher in obese than in non-obese patients. Chest wall contribution to respiratory system compliance differed widely between patients but was not predictable by their general characteristics.

Conclusions

Most respiratory mechanics features are similar in obese non-ARDS and non-obese ARDS patients, but end-expiratory esophageal pressure is higher in obese patients. A complete airway closure can be found in around 25% of critically ill patients ventilated with a PEEP of 5 cmH2O. Advanced explorations may allow to better characterize individual respiratory mechanics and adjust ventilation strategies in some patients.

Trial registration NCT03420417 ClinicalTrials.gov (February 5, 2018).
Anti-Ro52 positivity is associated with progressive interstitial lung disease in systemic sclerosis—an exploratory study
Authors: Hamberg Viggo , Sohrabian Azita , Volkmann Elizabeth R. , Wildt Marie , Löfdahl Anna , Wuttge Dirk M. , Hesselstrand Roger , Dellgren Göran , Westergren-Thorsson Gunilla , Rönnelid Johan , Andréasson Kristofer
Published: September 2023

Background

Interstitial lung disease (ILD) is the most common cause of death in patients with systemic sclerosis (SSc). Prognostic biomarkers are needed to identify SSc-ILD patients at risk for progressive pulmonary fibrosis. This study investigates autoantibodies measured in bronchoalveolar lavage (BAL) fluid and in serum in reference to the clinical disease course of SSc-ILD.

Methods

Fifteen patients with new onset SSc-ILD underwent bronchoscopy. Autoantibody levels were analyzed using addressable laser bead immunoassay from BAL fluid and the serum. In a separate longitudinal cohort of 43 patients with early SSc-ILD, autoantibodies in serum were measured at baseline and pulmonary function tests were performed at least 2 times over the course of at least 2 or more years. Linear mixed effect models were created to investigate the relationship between specific autoantibodies and progression of SSc-ILD. Finally, lung tissue from healthy controls and from subjects with SSc was analyzed for the presence of the Ro52 antigen using immunohistochemistry.

Results

Among SSc-ILD patients who were positive for anti-Ro52 (N = 5), 3 (60%) had enrichment of anti-Ro52 in BAL fluid at a ratio exceeding 50x. In the longitudinal cohort, 10/43 patients (23%) were anti-Ro52 positive and 16/43 (37%) were anti-scl-70 positive. Presence of anti-Scl-70 was associated with a lower vital capacity (VC) at baseline (-12.6% predicted VC [%pVC]; 95%CI: -25.0, -0.29; p = 0.045), but was not significantly associated with loss of lung function over time (-1.07%pVC/year; 95%CI: -2.86, 0.71; p = 0.230). The presence of anti-Ro52 was significantly associated with the loss of lung function over time (-2.41%pVC/year; 95% CI: -4.28, -0.54; p = 0.013). Rate of loss of lung function increased linearly with increasing anti-Ro52 antibody levels (-0.03%pVC per arbitrary units/mL and year; 95%CI: -0.05, -0.02; p < 0.001). Immunohistochemical staining localized the Ro52 antigen to alveolar M2 macrophages in peripheral lung tissue both in subjects with and without SSc.

Conclusions

This study suggests that antibodies targeting Ro52 are enriched in the lungs of patients with new-onset SSc-ILD, linking Ro52 autoimmunity to the pulmonary pathology of SSc. Clinical and immunohistochemical data corroborates these findings and suggest that anti-Ro52 may serve as a potential biomarker of progressive SSc-ILD.
SARS-CoV-2 infection induces epigenetic changes in the LTR69 subfamily of endogenous retroviruses
Authors: Arora Ankit , Kolberg Jan Eric , Srinivasachar Badarinarayan Smitha , Savytska Natalia , Munot Daksha , Müller Martin , Krchlíková Veronika , Sauter Daniel , Bansal Vikas
Published: September 2023

Accumulating evidence suggests that endogenous retroviruses (ERVs) play an important role in the host response to infection and the development of disease. By analyzing ChIP-sequencing data sets, we show that SARS-CoV-2 infection induces H3K27 acetylation of several loci within the LTR69 subfamily of ERVs. Using functional assays, we identified one SARS-CoV-2-activated LTR69 locus, termed Dup69, which exhibits regulatory activity and is responsive to the transcription factors IRF3 and p65/RELA. LTR69_Dup69 is located about 500 bp upstream of a long non-coding RNA gene (ENSG00000289418) and within the PTPRN2 gene encoding a diabetes-associated autoantigen. Both ENSG00000289418 and PTPRN2 showed a significant increase in expression upon SARS-CoV-2 infection. Thus, our study sheds light on the interplay of exogenous with endogenous viruses and helps to understand how ERVs regulate gene expression during infection.
Frequencies of mobilized colistin resistance (mcr-1, 2) genes in clinically isolated Escherichia coli; a cross sectional study
Authors: Mirzaei Bahman , Ebrahimi Aida , Hariri Bahareh , Sokouti Zahra , Kazemi Niloufar , Moradi Narges
Published: September 2023

Objective

Escherichia coli (E. coli) is an opportunistic bacterium, which is globally recognized for its high prevalence and antimicrobial resistance (AMR). The presence of colistin-resistant representative mcr- 1, 2 genes in multi-drug resistant (MDR) clinically isolated E. coli is the main goal of this survey. After biochemically and molecular confirmation tests, susceptibility testing, biofilm formation, and minimum inhibitory concentration to colistin were performed on 100 E. coli isolates. Subsequently, taking advantage of uniplex-PCR, the presence of some responsible genes (mcr- 1, mcr- 2) to colistin-resistant phenotypes in mentioned bacterium was assessed.

Results

Disc diffusion methods indicated that the highest resistance rate was against ampicillin (80.0%), and trimethoprim/sulfamethoxazole (63%). Among the E. coli isolates, 72 (72.0%) was determined as MDR, respectively. Moreover, 47 (47%) strains were determined as extreme beta-lactamase (ESBL) phenotypes. Among 41 slime-producing E. coli strains, 7 (17.07%), 14 (34.14%), and 20 (48.78%) strains exhibited high, moderate, and weak levels of biofilm formation, respectively. Fifty-nine (81.94%), and 1(100%) of MDR isolates were assessed as colistin resistant (MIC > 2) and susceptible (MIC ≤ 2) as well. In 26(36.11%) of colistin-resistant isolates and 1(1.38%) of colistin, susceptible isolate mcr-1 gene was found. There is no mcr- 2 gene was detected in isolates.

Conclusion

The diversity of high antibiotic-resistant rates could be avoided by developing appropriate healthcare policies and community awareness. Alarming resistance rates were observed in colistin and ampicillin, which should be taken into account in therapy guidelines.
Performance of plasma Aβ42/40, measured using a fully automated immunoassay, across a broad patient population in identifying amyloid status
Authors: Bun Shogyoku , Ito Daisuke , Tezuka Toshiki , Kubota Masahito , Ueda Ryo , Takahata Keisuke , Moriguchi Sho , Kurose Shin , Momota Yuki , Suzuki Natsumi , Morimoto Ayaka , Hoshino Yuka , Seki Morinobu , Mimura Yu , Shikimoto Ryo , Yamamoto Yasuharu , Hoshino Takayuki , Sato Yoshiaki , Tabuchi Hajime , Mimura Masaru
Published: September 2023

Background

Plasma biomarkers have emerged as promising screening tools for Alzheimer’s disease (AD) because of their potential to detect amyloid β (Aβ) accumulation in the brain. One such candidate is the plasma Aβ42/40 ratio (Aβ42/40). Unlike previous research that used traditional immunoassay, recent studies that measured plasma Aβ42/40 using fully automated platforms reported promising results. However, its utility should be confirmed using a broader patient population, focusing on the potential for early detection.

Methods

We recruited 174 participants, including healthy controls (HC) and patients with clinical diagnoses of AD, frontotemporal lobar degeneration, dementia with Lewy bodies/Parkinson’s disease, mild cognitive impairment (MCI), and others, from a university memory clinic. We examined the performance of plasma Aβ42/40, measured using the fully automated high-sensitivity chemiluminescence enzyme (HISCL) immunoassay, in detecting amyloid-positron emission tomography (PET)-derived Aβ pathology. We also compared its performance with that of Simoa-based plasma phosphorylated tau at residue 181 (p-tau181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL).

Results

Using the best cut-off derived from the Youden Index, plasma Aβ42/40 yielded an area under the receiver operating characteristic curve (AUC) of 0.949 in distinguishing visually assessed 18F-Florbetaben amyloid PET positivity. The plasma Aβ42/40 had a significantly superior AUC than p-tau181, GFAP, and NfL in the 167 participants with measurements for all four biomarkers. Next, we analyzed 99 participants, including only the HC and those with MCI, and discovered that plasma Aβ42/40 outperformed the other plasma biomarkers, suggesting its ability to detect early amyloid accumulation. Using the Centiloid scale (CL), Spearman’s rank correlation coefficient between plasma Aβ42/40 and CL was -0.767. Among the 15 participants falling within the CL values indicative of potential future amyloid accumulation (CL between 13.5 and 35.7), plasma Aβ42/40 categorized 61.5% (8/13) as Aβ-positive, whereas visual assessment of amyloid PET identified 20% (3/15) as positive.

Conclusion

Plasma Aβ42/40 measured using the fully automated HISCL platform showed excellent performance in identifying Aβ accumulation in the brain in a well-characterized cohort. This equipment may be useful for screening amyloid pathology because it has the potential to detect early amyloid pathology and is readily applied in clinical settings.
Exosomal miR-17-5p from human embryonic stem cells prevents pulmonary fibrosis by targeting thrombospondin-2
Authors: Liu Qun , Bi Youkun , Song Shaole , Zhu Keqi , Qiao Xinlong , Wang Huiwen , Ji Guangju
Published: September 2023

Background

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and irreversible lung disease characterized by pulmonary fibrosis and lung dysfunction, ultimately leading to respiratory failure. Many preclinical studies have investigated the therapeutic potential of stem cell-derived exosomes in this disease, particularly mesenchymal stem cell-derived exosomes. However, the effects of embryonic stem cell-derived exosomes in IPF remain unclear.

Methods

We established a bleomycin (BLM)-induced pulmonary fibrosis mice model and administered human embryonic stem cell exosomes (hESC-exo) from the first day after BLM treatment. The effects of hESC-exo were assessed by pulmonary function tests, biochemical analysis, histochemistry, quantitative real-time polymerase chain reaction (qPCR), and western blot (WB). RNA-seq was used to screen for the potential therapeutic targets of hESC-exo in fibrotic lungs; the identified signaling axis was characterized using a luciferase assay, qPCR, and WB.

Results

Results indicated hESC-exo administration notably alleviated inflammation, removed deposited collagen, and rescued alveolar architecture in the lungs of BLM-induced mice. In vivo and in vitro tests revealed that hESC-exo-derived miR-17-5p directly bound thrombospondin-2 (Thbs2) to regulate inflammation and fibrosis; thus, hESC-exo protected against BLM toxicity in the lungs via the miR-17-5p/Thbs2 axis.

Conclusion

These results suggest a promising new treatment for fibrosis-associated diseases.
Low-glucose culture environment can enhance the wound healing capability of diabetic adipose-derived stem cells
Authors: Li Chun-Wei , Young Tai-Horng , Wang Mu-Hui , Pei Ming-Ying , Hsieh Tsung-Yu , Hsu Chia-Lang , Cheng Nai-Chen
Published: September 2023

Background

Application of autologous adipose-derived stem cells (ASC) for diabetic chronic wounds has become an emerging treatment option. However, ASCs from diabetic individuals showed impaired cell function and suboptimal wound healing effects. We proposed that adopting a low-glucose level in the culture medium for diabetic ASCs may restore their pro-healing capabilities.

Methods

ASCs from diabetic humans and mice were retrieved and cultured in high-glucose (HG, 4.5 g/L) or low-glucose (LG, 1.0 g/L) conditions. Cell characteristics and functions were investigated in vitro. Moreover, we applied diabetic murine ASCs cultured in HG or LG condition to a wound healing model in diabetic mice to compare their healing capabilities in vivo.

Results

Human ASCs exhibited decreased cell proliferation and migration with enhanced senescence when cultured in HG condition in vitro. Similar findings were noted in ASCs derived from diabetic mice. The inferior cellular functions could be partially recovered when they were cultured in LG condition. In the animal study, wounds healed faster when treated with HG- or LG-cultured diabetic ASCs relative to the control group. Moreover, higher collagen density, more angiogenesis and cellular retention of applied ASCs were found in wound tissues treated with diabetic ASCs cultured in LG condition.

Conclusions

In line with the literature, our study showed that a diabetic milieu exerts an adverse effect on ASCs. Adopting LG culture condition is a simple and effective approach to enhance the wound healing capabilities of diabetic ASCs, which is valuable for the clinical application of autologous ASCs from diabetic patients.
First clinical experience with fractionated intracavitary radioimmunotherapy using [177Lu]Lu-6A10-Fab fragments in patients with glioblastoma: a pilot study
Authors: Roll Wolfgang , Müther Michael , Böning Guido , Delker Astrid , Warneke Nils , Gildehaus Franz-Josef , Schäfers Michael , Stummer Walter , Zeidler Reinhard , Reulen Hans-Jürgen , Stegger Lars
Published: September 2023

Background

Following resection and standard adjuvant radio- and chemotherapy, approved maintenance therapies for glioblastoma are lacking. Intracavitary radioimmunotherapy (iRIT) with 177Lu-labeled 6A10-Fab fragments targeting tumor-associated carbonic anhydrase XII and injected into the resection cavity offers a novel and promising strategy for improved tumor control.

Methods

Three glioblastoma patients underwent tumor resection followed by standard radio- and chemotherapy. These patients with stable disease following completion of standard therapy underwent iRIT on compassionate grounds. After surgical implantation of a subcutaneous injection reservoir with a catheter into the resection cavity, a leakage test with [99mTc]Tc-DTPA was performed to rule out leakage into other cerebral compartments. IRIT comprised three consecutive applications over three months for each patient, with 25%, 50%, 25% of the total activity injected. A dosimetry protocol was included with blood sampling and SPECT/CT of the abdomen to calculate doses for the bone marrow and kidneys as potential organs at risk.

Results

All three patients presented without relevant leakage after application of [99mTc]Tc-DTPA. Two patients underwent three full cycles of iRIT (592 MBq and 1228 MBq total activity). One patient showed histologically proven tumor progression after the second cycle (526 MBq total activity). No relevant therapy-associated toxicities or adverse events were observed. Dosimetry did not reveal absorbed doses above upper dose limits for organs at risk.

Conclusions

In first individual cases, iRIT with [177Lu]Lu-6A10-Fab appears to be feasible and safe, without therapy-related side effects. A confirmatory multicenter phase-I-trial was recently opened and is currently recruiting.
Process analysis and mitigation strategies for wetland degradation caused by increasing agricultural water demand: an ecology–economy nexus perspective
Authors: Jiang Lin , Wang Hui , Wang Saige , Zhang Wen
Published: September 2023

Background

Farmland expansion has played a major role in wetland degradation in Heilongjiang Province, China in recent decades. Farmland expansion increases the demands for water, thereby affecting wetland water cycles, and promoting the shrinkage of wetland areas and degradation of ecosystem functions. As an open system, agricultural production is limited by both ecological and socioeconomic conditions. However, our understanding of wetland degradation caused by farmland expansion from the perspective of the ecology–economy nexus is limited.

Methods

A correlation between farmland expansion and agricultural economic activities was established, and wetland degradation driven by agroeconomic activities was inversely derived using a multi-regional input–output (MRIO) analysis. We developed an ecology–economy nexus framework to explore the ecological process of the area and water demand tradeoffs between wetland degradation and farmland expansion, the economic process of wetland degradation driven by food consumption, and the nexus between the two processes. We finally explored strategies to mitigate wetland degradation due to increased agricultural water demand.

Results

Farmland expansion contributed to 93.76% of the total degraded wetland area. There was a significant negative correlation between wetland area and the water consumption for crop production, but no significant correlation between wetland area and the ecological footprint of croplands. The direct wetland degradation caused by local final demand accounted for 63.02%, while the indirect degradation caused by non-local final demand accounted for 36.98%. Hebei, Shandong, Liaoning, Inner Mongolia, and Shanghai were the top five provinces contributing to indirect wetland degradation in Heilongjiang. Our findings indicated that a mixed scenario combining water footprint reduction per unit yield with food export reduction could maximize wetland restoration while reducing local farmland–wetland competition for water.

Conclusions

Our research highlights the effects of economic processes in the agricultural sector on wetland degradation, and showed that the adjustment of food trade patterns can effectively promote wetland restoration.
Numerical and Experimental Analysis to Develop a SB6/H3 High Containment Level Concrete Median Barrier
Authors: Jeong Yoseok , Lee Ilkeun , Lee Jaeha , Kim Kyeongjin , Min Geunhyeong , Kim WooSeok
Published: September 2023

As the number of heavy vehicles on the road continues to increase, collisions involving heavy vehicles and concrete median barriers (CMB) occur more frequently than in the past. Consequently, there is a growing need for research into more stringent design standards and improvements to the current CMB and their performance under harsh conditions. High-performance CMB is required to in order to withstand such conditions. This paper presents the results of numerical simulations and full-scale field tests to develop a high-performance CMB. To facilitate the development of the high-performance CMB, the concept of a deformable CMB was applied to the rigid CMB. A new apparatus called the shock absorber composed of dowel bars surrounded by empty space were introduced to make the rigid CMB deformable. In order to prevent local failure at the top of the barrier from a sudden high increase in impact energy, the deformable CMB was strengthened by adding reinforcements and widening the top based on the results of numerical simulations. The full-scale field tests were conducted on the proposed deformable CMB and took into account three appraisal areas: (1) structural adequacy, (2) occupant risk, and (3) vehicle trajectory after collision. The results of these tests showed that the deformable CMB contained and redirected the vehicle without allowing it to penetrate or override the deformable CMB. No detached elements, fragmentation, or other debris from the barrier were present. Therefore, the proposed high-performance CMB fulfilled all of the requirements of the crash test guideline.
Synergist response of the Peach fruit fly, Bactrocera zonata (Saunders) to some ammonium based proteinaceous food bait attractants
Authors: Hasnain Muhammad , Saeed Shafqat , Ullah Unsar Naeem , Ullah Sami , Zaka Syed Muhammad
Published: September 2023

Background

Under the family Tephritidae, Bactrocera zonata (Saunders) is a serious pest, attacking fruits and vegetables causing large quantitative and qualitative damages throughout the world. Fruit flies require proteinaceous food for sexual maturation and egg development. Therefore, food bait attractants are frequently utilized for fruit fly detection, monitoring, mass trapping, and control. Using a Y-shape olfactometer (behavioral tests), we selected the best synthetic proteinaceous food bait attractants to volatiles identified by fruit fly antennae. The responses of B. zonata adults, male and female, to some ammonium compounds (ammonium acetate (AA), trimethylamine (TMA), and putrescine) that were mixed with certain food attractants were evaluated under laboratory conditions. Using flies ranging in age from 5 to 30 days, possible mixtures were discovered that might be useful in developing fruit fly attractants for both males and females. So, four base baits were developed by mixing protein hydrolysate with jaggery, papaya powder, kachri powder, potassium hydroxide (KOH), and guava pulp. Finally, thirty-two (32) synthetic blends were developed when the above four base baits were mixed with synthetic attractants.

Results

The olfactometer bioassay indicated that protein hydrolysate and jaggery-based baits were effective in attracting both male and female flies throughout their adult lives when combined with AA + putrescine (Bait 6) and AA + TMA + putrescine (Bait 8). Similarly, protein hydrolysate + guava pulp-based baits combined with AA + putrescine (Bait 6) and AA + TMA + putrescine (Bait 8) was effective in attracting both male and female flies from 5 to 30 days of age. The pH of all 32 synthetic blends was measured and ranged from 4.77 to 11.35.

Conclusions

According to our observation, the variation in pH may be due to differences in chemical composition between the attractants and food constituents. The pH of protein bait attractants may be an important factor in the attraction efficiency of B. zonata males and females.
Telehealth and cardiometabolic-based chronic disease: optimizing preventive care in forcibly displaced migrant populations
Authors: Nieto-Martínez Ramfis , De Oliveira-Gomes Diana , Gonzalez-Rivas Juan P. , Al-Rousan Tala , Mechanick Jeffrey I. , Danaei Goodarz ,   The Migrants Health Lown Scholar Program Team
Published: September 2023

The number of migrants, which includes forcibly displaced refugees, asylum seekers, and undocumented persons, is increasing worldwide. The global migrant population is heterogeneous in terms of medical conditions and vulnerability resulting from non-optimal metabolic risk factors in the country of origin (e.g., abnormal adiposity, dysglycemia, hypertension, and dyslipidemia), adverse travel conditions and the resulting stress, poverty, and anxiety, and varying effects of acculturation and access to healthcare services in the country of destination. Therefore, many of these migrants develop a high risk for cardiovascular disease and face the significant challenge of overcoming economic and health system barriers to accessing quality healthcare. In the host countries, healthcare professionals experience difficulties providing care to migrants, including cultural and language barriers, and limited institutional capacities, especially for those with non-legal status. Telehealth is an effective strategy to mitigate cardiometabolic risk factors primarily by promoting healthy lifestyle changes and pharmacotherapeutic adjustments. In this descriptive review, the role of telehealth in preventing the development and progression of cardiometabolic disease is explored with a specific focus on type 2 diabetes and hypertension in forcibly displaced migrants. Until now, there are few studies showing that culturally adapted telehealth services can decrease the burden of T2D and HTN. Despite study limitations, telehealth outcomes are comparable to those of traditional health care with the advantages of having better accessibility for difficult-to-reach populations such as forcibly displaced migrants and reducing healthcare associated costs. More prospective studies implementing telemedicine strategies to treat cardiometabolic disease burden in migrant populations are needed.
Popliteal tendon impingement as a cause of pain following total knee arthroplasty: a systematic review
Authors: Finsterwald Michael A. , Lu Victor , Andronic Octavian , Prosser Gareth H. , Yates Piers J. , Jones Christopher W.
Published: September 2023

Introduction

Popliteal tendon impingement (PTI) is an under-recognized cause of persistent pain following total knee arthroplasty (TKA). The purpose of the systematic review was to summarize and outline successful strategies in the diagnosis and management of PTI.

Methods

A systematic review following the PRISMA guidelines was performed for four databases: MEDLINE (Pubmed), Ovid EMBASE, Web of Science, and Cochrane Database. It was registered in the International Prospective Register for Systematic Reviews and Meta-analysis (PROSPERO) under the registration number: CRD42023398723. The risk of bias assessment was performed using the criteria of the methodological index for non-randomized studies (MINORS).

Results

A total of 8 studies were included. There were 2 retrospective case series and 6 case reports. The follow-up ranged from 6 to 30 months. Two studies described PTI as an intraoperative phenomenon during TKA with “snapping”; whilst 6 studies described indications and outcomes for arthroscopic tenotomy for PTI following TKA. In making the diagnosis, there was concurrence that the posterolateral pain should be focal and that dynamic ultrasonography and diagnostic injection play an important role. Two specific clinical tests have been described. There was no consistency regarding the need for imaging. There were no reports of instability following popliteal tendon tenotomy or other complications.

Conclusion

PTI should be suspected as a cause for persistent focal pain at the posterolateral knee following TKA. The diagnosis can be suspected on imaging and should be confirmed with dynamic ultrasonography and an ultrasound-guided diagnostic injection. An arthroscopic complete tenotomy of the tendon can reliably alleviate pain and relies on correct diagnosis. There is no evidence for clinically relevant negative biomechanical consequences following tenotomy.

Level of evidence

Systematic Review of Level IV and V studies.
Real-time service performances of BDS-3 and Galileo constellations with a linear satellite clock correction models
Authors: Li Haojun , Luojie Danzeng , Ding Huimin
Published: September 2023

In order to facilitate high-precision and real-time Precise Point Positioning (PPP), the International GNSS (Global Navigation Satellite System) Service (IGS), BDS-3 (BeiDou-3 Navigation Satellite System), and Galileo navigation satellite system (Galileo) have provided real-time satellite clock correction, which is updated at a high-frequency. However, the frequent updates pose the challenges of increasing the computational burden and compromising the timeliness of these correction parameters. To address this issue, an improved Real-Time Service (RTS) method is developed using an extrapolation algorithm and a linear model. The results indicate that a 1 h arc length of the satellite clock correction series is optimal for fitting a linear model of the RTS. With this approach, the 1 h extrapolation results for BDS-3 and Galileo are superior to 0.09 ns. Moreover, when these model coefficients are transmitted and updated at the intervals of 1, 2, 5, and 10 min, the corresponding PPP can converge at the centimeter-level. It is evident that these improved RTS methods outperform the current approach with high-frequency interval transmission, as they effectively mitigate the challenges associated with maintaining the timeliness of correction parameters.
Synthesis and clinical application of new drugs approved by FDA in 2022
Authors: Zhang Jing-Yi , Wang Ya-Tao , Sun Lu , Wang Sai-Qi , Chen Zhe-Sheng
Published: September 2023

The pharmaceutical industry had a glorious year in 2022, with a total of 37 new drugs including 20 new chemical entities (NCEs) and 17 new biological entities (NBEs) approved by the Food and Drug Administration (FDA). These drugs are mainly concentrated in oncology, central nervous system, antiinfection, hematology, cardiomyopathy, dermatology, digestive system, ophthalmology, MRI enhancer and other therapeutic fields. Of the 37 drugs, 25 (68%) were approved through an expedited review pathway, and 19 (51%) were approved to treat rare diseases. These newly listed drugs have unique structures and new mechanisms of action, which can serve as lead compounds for designing new drugs with similar biological targets and enhancing therapeutic efficacy. This review aims to outline the clinical applications and synthetic methods of 19 NCEs newly approved by the FDA in 2022, but excludes contrast agent (Xenon Xe-129). We believe that an in-depth understanding of the synthetic methods of drug molecules will provide innovative and practical inspiration for the development of new, more effective, and practical synthetic techniques. According to the therapeutic areas of these 2022 FDA-approved drugs, we have classified these 19 NCEs into seven categories and will introduce them in the order of their approval for marketing.
Chiral exceptional point and coherent suppression of backscattering in silicon microring with low loss Mie scatterer
Authors: Lee Hwaseob , Kecebas Ali , Wang Feifan , Chang Lorry , Özdemir Sahin K. , Gu Tingyi
Published: September 2023

Non-Hermitian systems with their spectral degeneracies known as exceptional points (EPs) have been explored for lasing, controlling light transport, and enhancing a sensor’s response. A ring resonator can be brought to an EP by controlling the coupling between its frequency degenerate clockwise and counterclockwise traveling modes. This has been typically achieved by introducing two or more nanotips into the resonator’s mode volume. While this method provides a route to study EP physics, the basic understanding of how the nanotips’ shape and size symmetry impact the system’s non-Hermicity is missing, along with additional loss from both in-plane and out-of-plane scattering. The limited resonance stability poses a challenge for leveraging EP effects for switches or modulators, which requires stable cavity resonance and fixed laser-cavity detuning. Here we use lithographically defined asymmetric and symmetric Mie scatterers, which enable subwavelength control of wave transmission and reflections without deflecting to additional radiation channels. We show that those pre-defined Mie scatterers can bring the system to an EP without post tuning, as well as enable chiral light transport within the resonator. Counterintuitively, the Mie scatterer results in enhanced quality factor measured on the transmission port, through coherently suppressing the backscattering from the waveguide surface roughness. The proposed device platform enables pre-defined chiral light propagation and backscattering-free resonances, needed for various applications such as frequency combs, solitons, sensing, and other nonlinear optical processes such as photon blockade, and regenerative oscillators.

Graphical Abstract
Real-time monitoring of an endogenous Fgf8a gradient attests to its role as a morphogen during zebrafish gastrulation
Authors: Harish Rohit Krishnan , Gupta Mansi , Zöller Daniela , Hartmann Hella , Gheisari Ali , Machate Anja , Hans Stefan , Brand Michael
Published: September 2023

Morphogen gradients impart positional information to cells in a homogenous tissue field. Fgf8a, a highly conserved growth factor, has been proposed to act as a morphogen during zebrafish gastrulation. However, technical limitations have so far prevented direct visualization of the endogenous Fgf8a gradient and confirmation of its morphogenic activity. Here, we monitor Fgf8a propagation in the developing neural plate using a CRISPR/Cas9-mediated EGFP knock-in at the endogenous fgf8a locus. By combining sensitive imaging with single-molecule fluorescence correlation spectroscopy, we demonstrate that Fgf8a, which is produced at the embryonic margin, propagates by diffusion through the extracellular space and forms a graded distribution towards the animal pole. Overlaying the Fgf8a gradient curve with expression profiles of its downstream targets determines the precise input-output relationship of Fgf8a-mediated patterning. Manipulation of the extracellular Fgf8a levels alters the signaling outcome, thus establishing Fgf8a as a bona fide morphogen during zebrafish gastrulation. Furthermore, by hindering Fgf8a diffusion, we demonstrate that extracellular diffusion of the protein from the source is crucial for it to achieve its morphogenic potential.
An inducible germ cell ablation chicken model for high-grade germline chimeras
Authors: Chen Yi-Chen , Saito Daisuke , Suzuki Takayuki , Takemoto Tatsuya
Published: September 2023

Chicken embryos are a powerful and widely used animal model in developmental biology studies. Since the development of CRISPR technology, gene-edited chickens have been generated by transferring primordial germ cells (PGCs) into recipients after genetic modifications. However, low inheritance caused by competition between host germ cells and the transferred cells is a common complication and greatly reduces production efficiency. Here, we generated a gene-edited chicken, in which germ cells can be ablated in a drug-dependent manner, as recipients for gene-edited PGC transfer. We used the nitroreductase/metronidazole (NTR/Mtz) system for cell ablation, in which nitroreductase produces cytotoxic alkylating agents from administered metronidazole, causing cell apoptosis. The chicken Vasa homolog (CVH) gene locus was used to drive the expression of the nitroreductase gene in a germ cell-specific manner. In addition, a fluorescent protein gene, mCherry, was also placed in the CVH locus to visualize the PGCs. We named this system ‘germ cell-specific autonomous removal induction’ (gSAMURAI). gSAMURAI chickens will be an ideal recipient to produce offspring derived from transplanted exogenous germ cells.
Blood levels of neurofilament light are associated with disease progression in a mouse model of spinocerebellar ataxia type 3
Authors: Mengel David , Wellik Isabel G. , Schuster Kristen H. , Jarrah Sabrina I. , Wacker Madeleine , Ashraf Naila S. , Öz Gülin , Synofzik Matthis , Costa Maria do Carmo , McLoughlin Hayley S.
Published: September 2023

Increased neurofilament light (NfL; NEFL) protein in biofluids is reflective of neurodegeneration and has gained interest as a biomarker across neurodegenerative diseases. In spinocerebellar ataxia type 3 (SCA3), the most common dominantly inherited ataxia, patients exhibit progressive NfL increases in peripheral blood when becoming symptomatic, and NfL remains stably elevated throughout further disease course. However, progressive NfL changes are not yet validated in relevant preclinical SCA3 animal models, hindering its application as a biomarker during therapeutic development. We used ultra-sensitive single-molecule array (Simoa) to measure blood NfL over disease progression in YACQ84 mice, a model of SCA3, assessing relationships with measures of disease severity including age, CAG repeat size and magnetic resonance spectroscopy. YACQ84 mice exhibited plasma NfL increases that were concomitant with ataxia-related motor deficits as well as increased serum NfL, which correlated with previously established neurometabolite abnormalities, two relevant measures of disease in patients with SCA3. Our findings establish the progression of NfL increases in the preclinical YACQ84 mouse, further supporting the utility of blood NfL as a peripheral neurodegeneration biomarker and informing on coinciding timelines of different measures of SCA3 pathogenesis.
History-dependent muscle resistance to stretch remains high after small, posturally relevant pre-movements
Authors: Horslen Brian C. , Milburn Gregory N. , Blum Kyle P. , Simha Surabhi N. , Campbell Kenneth S. , Ting Lena H.
Published: September 2023

The contributions of intrinsic muscle fiber resistance during mechanical perturbations to standing and other postural behaviors are unclear. Muscle short-range stiffness is known to vary depending on the current level and history of the muscle's activation, as well as the muscle's recent movement history; this property has been referred to as history dependence or muscle thixotropy. However, we currently lack sufficient data about the degree to which muscle stiffness is modulated across posturally relevant characteristics of muscle stretch and activation. We characterized the history dependence of muscle's resistance to stretch in single, permeabilized, activated, muscle fibers in posturally relevant stretch conditions and activation levels. We used a classic paired muscle stretch paradigm, varying the amplitude of a ‘conditioning’ triangular stretch–shorten cycle followed by a ‘test’ ramp-and-hold imposed after a variable inter-stretch interval. We tested low (<15%), intermediate (15–50%) and high (>50%) muscle fiber activation levels, evaluating short-range stiffness and total impulse in the test stretch. Muscle fiber resistance to stretch remained high at conditioning amplitudes of <1% optimal fiber length, L0, and inter-stretch intervals of >1 s, characteristic of healthy standing postural sway. An ∼70% attenuation of muscle resistance to stretch was reached at conditioning amplitudes of >3% L0 and inter-stretch intervals of <0.1 s, characteristic of larger, faster postural sway in balance-impaired individuals. The thixotropic changes cannot be predicted solely on muscle force at the time of stretch. Consistent with the disruption of muscle cross-bridges, muscle resistance to stretch during behavior can be substantially attenuated if the prior motion is large enough and/or frequent enough.
Novel approaches for assessing acclimatization in birds reveal seasonal changes in peripheral heat exchange and thermoregulatory behaviors
Authors: Zuluaga Juan D. , Danner Raymond M.
Published: September 2023

Using thermography and behavioral analyses, we found that heat exchange and thermoregulatory behaviors changed seasonally in chipping sparrows (Spizella passerina). Studies on seasonal acclimatization in birds have primarily involved metabolic measurements, few of which have investigated behaviors, and none have investigated changes in peripheral heat exchange. We captured chipping sparrows in the winter and summer of 2022 in Wilmington, North Carolina, USA, and we collected thermal images of these birds at 15.0, 27.5 and 40.0°C. We found that heat dissipation through the bill and legs changed seasonally, but surprisingly both were higher in winter than in summer. We found that heat dissipating behaviors were more common in winter, whereas heat conserving behaviors were more common in summer, and that behaviors associated with resource costs (e.g. panting) or predation risk (e.g. bill tucking) showed the most distinct differences between seasons. Meanwhile, low-cost and low-risk postural adjustments (e.g. feather adjustments and tarsus exposure) did not vary as strongly between seasons but followed similar trends. The seasonal adjustments to behaviors suggest that non-acclimatized birds must use costly thermoregulatory behaviors more frequently than acclimatized birds. The use of thermography resulted in the discovery of one completely novel behavior, and the first detection of a known behavior in a new species. Both novel behaviors aided in evaporative heat loss and occurred more commonly in winter, supporting the presence of seasonal acclimatization as evidenced by behavioral adjustments. These results provide novel insights into the process of acclimatization and suggest a role for behavioral adjustments in seasonal acclimatization.
Cardiorespiratory physiology and swimming capacity of Atlantic salmon (Salmo salar) at cold temperatures
Authors: Porter Emma S. , Gamperl A. Kurt
Published: September 2023

We investigated how acclimation to 8, 4 and 1°C, and acute cooling from 8  to 1°C, affected the Atlantic salmon's aerobic and anaerobic metabolism, and cardiac function, during a critical swim speed (Ucrit) test. This study revealed several interesting temperature-dependent effects. First, while differences in resting heart rate (fH) between groups were predictable based on previous research (range ∼28–65 beats  min−1), with values for 1°C-acclimated fish slightly higher than those of acutely exposed conspecifics, the resting cardiac output () of 1°C-acclimated fish was much lower and compensated for by a higher resting blood oxygen extraction (ṀO2/). In contrast, the acutely exposed fish had a ∼2-fold greater resting stroke volume (VS) compared with that of the other groups. Second, increases in fH (1.2- to 1.4-fold) contributed little to during the Ucrit test, and the contributions of (VS) versus ṀO2/ to aerobic scope (AS) were very different in the two groups tested at 1°C (1°C-acclimated and 8–1°C fish). Finally, Ucrit was 2.08 and 1.69 body lengths (BL) s−1 in the 8 and 4°C-acclimated groups, but only 1.27 and 1.44 BL s−1 in the 1°C-acclimated and 8–1°C fish, respectively – this lower value in 1°C versus 8–1°C fish despite higher values for maximum metabolic rate and AS. These data: support recent studies which suggest that the capacity to increase fH is constrained at low temperatures; show that cardiorespiratory function at cold temperatures, and its response to increased demands, depends on exposure duration; and suggest that AS does not constrain swimming capacity in salmon when chronically exposed to temperatures approaching their lower limit.
Comparison of acoustic particle acceleration detection capabilities in three shark species
Authors: Nieder Carolin , Gibbs Brendan J. , Rapson Jimmy , McLay Jessica , Montgomery John C. , Radford Craig A.
Published: September 2023

Behavioural studies have shown that sharks are capable of directional orientation to sound. However, only one previous experiment addresses the physiological mechanisms of directional hearing in sharks. Here, we used a directional shaker table in combination with the auditory evoked potential (AEP) technique to understand the broadscale directional hearing capabilities in the New Zealand carpet shark (Cephaloscyllium isabellum), rig shark (Mustelus lenticulatus) and school shark (Galeorhinus galeus). The aim of this experiment was to test if sharks are more sensitive to vertical (z-axis) or head-to-tail (x-axis) accelerations, and whether there are any differences between species. Our results support previous findings, suggesting that shark ears can receive sounds from all directions. Acceleration detection bandwidth was narrowest for the carpet shark (40–200 Hz), and broader for rig and school sharks (40–800 Hz). Greatest sensitivity bands were 40–80 Hz for the carpet shark, 100–200 Hz for the rig and 80–100 Hz for the school shark. Our results indicate that there may be differences in directional hearing abilities among sharks. The bottom-dwelling carpet shark was equally sensitive to vertical and head-to-tail particle accelerations. In contrast, both benthopelagic rig and school sharks appeared to be more sensitive to vertical accelerations at frequencies up to 200 Hz. This is the first study to provide physiological evidence that sharks may differ in their directional hearing and sound localisation abilities. Further comparative physiological and behavioural studies in more species with different lifestyles, habitats and feeding strategies are needed to further explore the drivers for increased sensitivity to vertical accelerations among elasmobranchs.