bluuebunny/crossref_metadata_2025 huggingface dataset:
Gelatin maleimide microgels for hematopoietic progenitor cell encapsulation
Authors: Thompson Gunnar B. , Gilchrist Aidan E. , Lam Vincent M. , Nunes Alison C. , Payan Brittany A. , Mora‐Boza Ana , Serrano Julio F. , García Andrés J. , Harley Brendan A. C.
Published: June 2024

Hematopoietic stem cells (HSCs) are the apical cells of the hematopoietic system, giving rise to cells of the blood and lymph lineages. HSCs reside primarily within bone marrow niches that contain matrix and cell‐derived signals that help inform stem cell fate. Aspects of the bone marrow microenvironment have been captured in vitro by encapsulating cells within hydrogel matrices that mimic native mechanical and biochemical properties. Hydrogel microparticles, or microgels, are increasingly being used to assemble granular biomaterials for cell culture and noninvasive delivery applications. Here, we report the optimization of a gelatin maleimide hydrogel system to create monodisperse gelatin microgels via a flow‐focusing microfluidic process. We report characteristic hydrogel stiffness, stability, and swelling characteristics as well as encapsulation of murine hematopoietic stem and progenitor cells, and mesenchymal stem cells within microgels. Microgels support cell viability, confirming compatibility of the microfluidic encapsulation process with these sensitive bone marrow cell populations. Overall, this work presents a microgel‐based gelatin maleimide hydrogel as a foundation for future development of a multicellular artificial bone marrow culture system.
The role of different physical function tests for the prediction of fracture risk in older women
Authors: Gregori Giulia , Johansson Lisa , Axelsson Kristian F. , Jaiswal Raju , Litsne Henrik , Larsson Berit A. M. , Lorentzon Mattias
Published: June 2024

Background

Physical function is an important risk factor for fracture. Previous studies found that different physical tests (e.g., one‐leg standing [OLS] and timed up and go [TUG]) predict fracture risk. This study aimed to determine which physical function test is the most optimal independent predictor of fracture risk, together with clinical risk factors (CRFs) used in fracture risk assessment (FRAX) and bone mineral density (BMD).

Methods

In total, 2321 women out of the included 3028 older women, aged 77.7 ± 1.6 (mean ± SD), in the Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures study had complete data on all physical function tests and were included in the analysis. At baseline, hand grip strength, OLS, TUG, walking speed and chair stand tests were performed. All incident fractures were confirmed by X‐ray or review of medical records and subsequently categorized as major osteoporotic fractures (MOFs), hip fractures and any fracture. Multivariate Cox regression (hazard ratios [HRs] and 95% confidence intervals [CIs]) analyses were performed with adjustments for age, body mass index (BMI), FRAX CRFs, femoral neck BMD and all physical function tests as predictors both individually and simultaneously. Receiver operating characteristic (ROC) analyses and Fine and Gray analyses were also performed to investigate associations between physical function and incident fractures.

Results

OLS was the only physical function test to be significantly and independently associated with increased risk of any fracture (HR 1.13 [1.04–1.23]), MOF (HR 1.15 [1.04–1.26]) and hip fracture (HR 1.34 [1.11–1.62]). Adjusting for age, BMI, CRFs and femoral neck BMD did not materially alter these associations. ROC analysis for OLS, together with age, BMI, femoral neck BMD and CRFs, yielded area under the curve values of 0.642, 0.647 and 0.732 for any fracture, MOF and hip fracture, respectively. In analyses considering the competing risk of death, OLS was the only physical function test consistently associated with fracture outcomes (subhazard ratio [SHR] 1.10 [1.01–1.19] for any fracture, SHR 1.11 [1.00–1.22] for MOF and SHR 1.25 [1.03–1.50] for hip fracture). Walking speed was only independently associated with the risk of hip fracture in all Cox regression models and in the Fine and Gray analyses.

Conclusions

Among the five physical function tests, OLS was independently associated with all fracture outcomes, even after considering the competing risk of death, indicating that OLS is the most reliable physical function test for predicting fracture risk in older women.
Swallowing muscle mass contributes to post‐stroke dysphagia in ischemic stroke patients undergoing mechanical thrombectomy
Authors: Pinho João , Meyer Tareq , Schumann‐Werner Beate , Becker Johanna , Tauber Simone , Nikoubashman Omid , Wiesmann Martin , Schulz Jörg B. , Werner Cornelius J. , Reich Arno
Published: June 2024

Background

Neurogenic dysphagia is a frequent complication of stroke and is associated with aspiration pneumonia and poor outcomes. Although ischaemic lesion location and size are major determinants of the presence and severity of post‐stroke dysphagia, little is known about the contribution of other acute stroke‐unrelated factors. We aimed to analyse the impact of swallowing and non‐swallowing muscles measurements on swallowing function after large vessel occlusion stroke.

Methods

This retrospective study was based on a prospective registry of consecutive ischaemic stroke patients. Patients who underwent mechanical thrombectomy between July 2021 and June 2022 and received a flexible endoscopic evaluation of swallowing (FEES) within 5 days after admission were included. Demographic, anthropometric, clinical, and imaging data were collected from the registry. The cross‐sectional areas (CSA) of selected swallowing muscles (as a surrogate marker for swallowing muscle mass) and of cervical non‐swallowing muscles were measured in computed tomography. Skeletal muscle index (SMI) was calculated and used as a surrogate marker for whole body muscle mass. FEES parameters, namely, Functional Oral Intake Scale (FOIS, as a surrogate marker for dysphagia presence and severity), penetration aspiration scale, and the presence of moderate‐to‐severe pharyngeal residues were collected from the clinical records. Univariate and multivariate ordinal and logistic regression analyses were performed to analyse if total CSA of swallowing muscles and SMI were associated with FEES parameters.

Results

The final study population consisted of 137 patients, 59 were female (43.1%), median age was 74 years (interquartile range 62–83), median baseline National Institutes of Health Stroke Scale score was 12 (interquartile range 7–16), 16 patients had a vertebrobasilar occlusion (11.7%), and successful recanalization was achieved in 127 patients (92.7%). Both total CSA of swallowing muscles and SMI were significantly correlated with age (rho = −0.391, P < 0.001 and rho = −0.525, P < 0.001, respectively). Total CSA of the swallowing muscles was independently associated with FOIS (common adjusted odds ratio = 1.08, 95% confidence interval = 1.01–1.16, P = 0.029), and with the presence of moderate‐to‐severe pharyngeal residues for puree consistencies (adjusted odds ratio = 0.90, 95% confidence interval = 0.81–0.99, P = 0.036). We found no independent association of SMI with any of the FEES parameters.

Conclusions

Baseline swallowing muscle mass contributes to the pathophysiology of post‐stroke dysphagia. Decreasing swallowing muscle mass is independently associated with increasing severity of early post‐stroke dysphagia and with increased likelihood of moderate‐to‐severe pharyngeal residues.
GDF‐15 is associated with sarcopenia and frailty in acutely admitted older medical patients
Authors: Kamper Rikke S. , Nygaard Hanne , Praeger‐Jahnsen Louis , Ekmann Anette , Ditlev Sisse Bolm , Schultz Martin , Hansen Sofie Krarup , Hansen Pernille , Pressel Eckart , Suetta Charlotte
Published: June 2024

Background

Growth differentiation factor‐15 (GDF‐15) has been associated with senescence, lower muscle strength, and physical performance in healthy older people. Still, it is not clear whether GDF‐15 can be utilized as a biomarker of sarcopenia and frailty in the early stages of hospitalization. We investigated the association of plasma GDF‐15 with sarcopenia and frailty in older, acutely admitted medical patients.

Methods

The present study is based on secondary analyses of cross‐sectional data from the Copenhagen PROTECT study, a prospective cohort study including 1071 patients ≥65 years of age admitted to the acute medical ward at Copenhagen University Hospital, Bispebjerg, Denmark. Muscle strength was assessed using handgrip strength, and lean mass was assessed using direct segmental multifrequency bioelectrical impedance analyses and used to clarify the potential presence of sarcopenia defined according to guidelines from the European Working Group on Sarcopenia in Older People. Frailty was evaluated using the Clinical Frailty Scale. Plasma GDF‐15 was measured using electrochemiluminescence assays from Meso Scale Discovery (MSD, Rockville, MD, USA).

Results

We included 1036 patients with completed blood samples (mean age 78.9 ± 7.8 years, 53% female). The median concentration of GDF‐15 was 2669.3 pg/mL. Systemic GDF‐15 was significantly higher in patients with either sarcopenia (P < 0.01) or frailty (P < 0.001) compared with patients without the conditions. Optimum cut‐off points of GDF‐15 relating to sarcopenia and frailty were 1541 and 2166 pg/mL, respectively.

Conclusions

Systemic GDF‐15 was higher in acutely admitted older medical patients with sarcopenia and frailty compared with patients without. The present study defined the optimum cut‐off for GDF‐15, related to the presence of sarcopenia and frailty, respectively. When elevated above the derived cutoffs, GDF‐15 was strongly associated with frailty and sarcopenia in both crude and fully adjusted models.
Changes in pre‐haemodialysis serum creatinine levels over 2 years and long‐term survival in maintenance haemodialysis
Authors: Kang Seok Hui , Kim Gui Ok , Kim Bo Yeon , Son Eun Jung , Do Jun Young , Lee Jung Eun
Published: June 2024

Background

Pre‐haemodialysis (HD) serum creatinine levels are reliable and inexpensive markers of muscle mass and important predictors of survival in patients with stable chronic HD. We aimed to assess whether changes in pre‐HD serum creatinine levels during a 2‐year period are linked to long‐term patient survival.

Methods

We retrospectively analysed patients enrolled in a periodic HD quality assessment program. Of the 21 846 participants in the fourth HD quality assessment program, 13 765 were presented in the fifth, of which 10 299 eligible patients were included in this study. We assessed the change in serum creatinine levels over 2 years. The patients were categorized into the following three groups: stable group (patients with change in serum creatinine < 1 mg/dL during 2 years of HD, n = 5664), increasing group (patients with increase in serum creatinine ≥ 1 mg/dL, n = 2419) and decreasing group (patients with decrease in serum creatinine ≥ 1 mg/dL, n = 2216).

Results

The duration of HD at baseline was 62–83 months, with diabetic kidney disease being the most common cause of kidney failure in 36.4% of patients. The 5‐year patient survival rates in the stable, increasing and decreasing groups were 69.1%, 71.3% and 66.8%, respectively. The decreasing group had poorer patient survival than the other two groups (P = 0.083 for stable vs. increasing group; P = 0.011 for stable vs. decreasing group; P < 0.001 for increasing vs. decreasing group). There was no significant difference in the cardiovascular event‐free survival rate among the three groups. Multivariable Cox regression analyses revealed the highest hazard ratio (HR) for mortality in the decreasing group (HR 1.33, 95% confidence interval [CI] 1.21–1.45, P < 0.001 vs. stable group; HR 1.50, 95% CI 1.34–1.69, P < 0.001 vs. increasing group). The increasing group exhibited a lower risk of mortality than the stable group (HR 0.88, 95% CI 0.81–0.97, P = 0.008). Subgroup analyses based on age, HD vintage, sex, Charlson comorbidity index score, presence of diabetes and baseline serum creatinine level tertiles revealed that the decreasing group exhibited the highest mortality among all subgroups.

Conclusions

Our results demonstrate that changes in pre‐HD serum creatinine levels over 2 years of HD were associated with all‐cause mortality in patients undergoing HD. This finding suggests a simple and promising approach for clinicians in the prognosis and management of patients undergoing HD.
Pseudoaneurysm of the mitral‐aortic intervalvular fibrosa in children diagnosed by echocardiography: Two case reports
Authors: Liu Xiaofang , Liu Qinghua , Miao Lili , Yan Yuxi , Pang Huanping , Li Xianjun , Zou Qiushi
Published: June 2024

Pseudoaneurysm of the mitral‐aortic intervalvular fibrosa is rare, particularly in children, and is potentially fatal. This article presents two cases of pediatric mitral‐aortic intervalvular fibrosa pseudoaneurysm: one secondary to infective endocarditis and the other confirmed to be congenital in nature. The characteristic echocardiographic manifestations of mitral‐aortic intervalvular fibrosa pseudoaneurysm demonstrated in this study will enhance diagnostic efficacy and guide early clinical intervention.
Complete detection of FR1 to FR3 primer‐based PCR patterns of immunoglobulin heavy chain rearrangement in the BIOMED‐2 protocol is associated with poor prognosis in patients with diffuse large B‐cell lymphoma
Authors: Yabushita Tomohiro , Shimomura Yoshimitsu , Maruoka Hayato , Katoh Daisuke , Yamashita Daisuke , Satake Hironaga , Hiramoto Nobuhiro , Yoshioka Satoshi , Yonetani Noboru , Nishikori Momoko , Morimoto Takeshi , Imai Yukihiro , Ishikawa Takayuki
Published: June 2024

Somatic hypermutations (SHMs) in the variable region (VH) of the immunoglobulin heavy chain (IgH) gene are common in diffuse large B‐cell lymphoma (DLBCL). Recently, IgH VH SHMs have become known as immunogenic neoantigens, but few studies have evaluated the prognostic impact of the frequency of VH SHMs in DLBCL. The BIOMED‐2 protocol is the gold standard polymerase chain reaction (PCR) for clonality analysis in lymphoid malignancies, but can produce false negatives due to the presence of IgH VH SHMs. To overcome this problem, three primer sets were designed for the three framework regions (FR1, FR2, and FR3). We evaluated the predictive value of this PCR pattern in patients with DLBCL. To evaluate the prognostic impact of complete detection of the clonal amplifications (VHFR1–JH, VHFR2–JH, and VHFR3–JH) in the BIOMED‐2 protocol, we retrospectively analyzed 301 DLBCL patients who were initially treated with anthracycline‐based immunochemotherapy. Complete detection of the FR1 to FR3 primer‐based IgH VH PCR patterns in the BIOMED‐2 protocol was associated with low frequency of VH SHMs (p < 0.001). Patients who were positive for all these three PCRs (n = 79) were significantly associated with shorter 5‐year overall survival (OS; 54.2% vs. 73.2%; p = 0.002) and progression‐free survival (PFS; 34.3% vs. 59.3%; p < 0.001) compared to patients with other PCR patterns (n = 202). Specifically, the successful FR3‐JH detection was associated with significantly worse OS (p < 0.001) and PFS (p < 0.001). PCR patterns of complete IgH rearrangement using the BIOMED‐2 protocol are clinically meaningful indicators for prognostic stratification of DLBCL patients.
Case series: Congenital enterovirus infection‐associated haemophagocytic lymphohistiocytosis and subsequent neutropaenia
Authors: Penner Justin , Burns James E. , Breuer Judith , Gilmour Kimberly C. , Bamford Alasdair , Rao Anupama
Published: June 2024

Congenital enterovirus infection can be associated with a pro‐inflammatory state triggering haemophagocytic lymphohistiocytosis (HLH). Enteroviruses are also known to cause transient neutropenia in healthy children. Two infants presented with temperature instability, lethargy, thrombocytopaenia, hepatosplenomegaly and evidence of hyperinflammation in the setting of perinatal maternal rash and household contacts with gastrointestinal symptoms. Whilst HLH was successfully treated in both, protracted neutropenia persisted. Immune dysregulation with enterovirus in the neonatal period can provoke the generation of autoantibodies to hematologic cells giving rise to conditions such as autoimmune neutropenia. Sustained neutropaenia, after resolution of secondary infectious forms of HLH, requires investigation for underlying aetiologies.
Successful treatment of refractory donor‐specific‐human leukocyte antigen‐antibody‐induced primary graft‐failure with daratumumab: A case report
Authors: Lesan Vadim , Melivadze Ketevani , Hein Johannes , Ahlgrimm Manfred , Schunk Stefan , Bewarder Moritz , Christofyllakis Konstantinos , Bittenbring Joerg Thomas , Thurner Lorenz
Published: June 2024

Donor‐specific anti‐human leukocyte antigen (HLA) antibodies represent a main cause of primary graft failure specifically in the setting of haploidentical stem cell transplantation. Newer therapy strategies including daratumumab could overcome some of these limitations. We describe the case of a patient with refractory acute myeloid leukemia. A haploidentical allogeneic stem cell transplantation was therefore initiated. HLA‐antibodies testing revealed a high titer of donor‐specific antibodies. First desensitization therapy failed, resulting in primary graft failure. A second desensitization regimen including plasmapheresis, intravenous gammaglobulins, and daratumumab resulted in good engraftment. Daratumumab is a promising and effective desensitization option in high‐risk allo‐sensitized patients undergoing haploidentical stem cell transplantation.
Newborn auditory brainstem response and sudden infant death syndrome
Authors: Maylott Sarah E. , Zeng Guangyu , Leung Tiffany S. , Montenegro Catalina Sanchez , Barrios Alexia , Malik Arushi , Delgado Rafael E. , Delgado Christine F. , Simpson Elizabeth A.
Published: June 2024

Sudden infant death syndrome (SIDS)—the sudden and unexplained death of a seemingly healthy infant, <1 year old—may be associated with abnormalities in the brain regions that underlie breathing and arousal during sleep. While post‐mortem studies suggest abnormalities in SIDS infants' brainstems, there are no studies of these infants' brainstem function before death. One way to assess the function of the brainstem is with auditory brainstem response (ABR), a routine hearing‐screening method that noninvasively measures the brainstem's response to sound. We hypothesize that anomalies in newborns' ABR measures may predict SIDS. Indeed, previous studies identified abnormalities in ABR characteristics in small samples of near‐miss SIDS infants hospitalized for infant apnea syndrome. However, there is a need to examine the ABRs of infants who died of SIDS. Therefore, in the current study, we propose integrating two secondary datasets to examine newborns' ABRs (N = 156,972), including those who later died of SIDS (n = ~42; .27 out of every 1000 infants), using existing archived records of neonatal ABR results from a sample of newborns born in Florida. We hypothesize that infants who die from SIDS are more likely than non‐SIDS infants to have abnormal ABRs as newborns. Understanding the association between SIDS and ABR may facilitate more accurate identification of an infant's risk for SIDS at birth, enabling increased monitoring, which may facilitate interventions and improve survivorship.
Effect of hyperuricemia on paroxysmal atrial fibrillation after catheter ablation and influence of alcohol consumption
Authors: Shimojo Kazuki , Morishima Itsuro , Morita Yasuhiro , Kanzaki Yasunori , Miyazawa Hiroyuki , Watanabe Naoki , Yoshioka Naoki , Shibata Naoki , Arao Yoshihito , Yamauchi Ryota , Ohi Takuma , Goto Hiroki , Karasawa Hoshito , Okumura Kenji
Published: June 2024

Background

Evidence regarding the association between hyperuricemia and arrhythmia recurrence after catheter ablation for paroxysmal atrial fibrillation (AF) is scarce. We investigated whether hyperuricemia predicts arrhythmia recurrence after catheter ablation for paroxysmal AF and the relationship between hyperuricemia and alcohol consumption in AF recurrence.

Methods

Patients who underwent catheter ablation for paroxysmal AF were divided into the hyperuricemia (index serum uric acid [UA] >7.0 mg/dL; n = 114) and control (UA ≤7.0 mg/dL; n = 609) groups and were followed for a median of 24 (12–48) months after ablation.

Results

The hyperuricemia group had more patients with an alcohol intake of ≥20 g/day (33.3% vs. 22.7%, p = .017) and a lower incidence of AF‐free survival (p = .019). Similarly, those with an alcohol intake of ≥20 g/day had a lower incidence of AF‐free survival than other patients. Multivariate Cox regression analysis revealed the following independent predictors of AF recurrence (adjusted hazard ratio, 95% confidence interval): hyperuricemia (1.64, 1.12–2.40), female gender (1.91, 1.36–2.67), brain natriuretic peptide level >100 pg/mL (1.59, 1.14–2.22), and alcohol consumption ≥20 g/day (1.49, 1.03–2.15) (all p < .05). In addition, causal mediation analysis revealed that alcohol consumption of ≥20 g/day directly affected AF recurrence, independent of hyperuricemia.

Conclusions

Patients with hyperuricemia may be at a high risk of arrhythmia recurrence after catheter ablation for paroxysmal AF. Although high alcohol consumption may contribute to increased UA levels, the presence of hyperuricemia may independently predict AF recurrence.
Performance of two large language models for data extraction in evidence synthesis
Authors: Konet Amanda , Thomas Ian , Gartlehner Gerald , Kahwati Leila , Hilscher Rainer , Kugley Shannon , Crotty Karen , Viswanathan Meera , Chew Robert
Published: June 2024

Accurate data extraction is a key component of evidence synthesis and critical to valid results. The advent of publicly available large language models (LLMs) has generated interest in these tools for evidence synthesis and created uncertainty about the choice of LLM. We compare the performance of two widely available LLMs (Claude 2 and GPT‐4) for extracting pre‐specified data elements from 10 published articles included in a previously completed systematic review. We use prompts and full study PDFs to compare the outputs from the browser versions of Claude 2 and GPT‐4. GPT‐4 required use of a third‐party plugin to upload and parse PDFs. Accuracy was high for Claude 2 (96.3%). The accuracy of GPT‐4 with the plug‐in was lower (68.8%); however, most of the errors were due to the plug‐in. Both LLMs correctly recognized when prespecified data elements were missing from the source PDF and generated correct information for data elements that were not reported explicitly in the articles. A secondary analysis demonstrated that, when provided selected text from the PDFs, Claude 2 and GPT‐4 accurately extracted 98.7% and 100% of the data elements, respectively. Limitations include the narrow scope of the study PDFs used, that prompt development was completed using only Claude 2, and that we cannot guarantee the open‐source articles were not used to train the LLMs. This study highlights the potential for LLMs to revolutionize data extraction but underscores the importance of accurate PDF parsing. For now, it remains essential for a human investigator to validate LLM extractions.
Long‐term survivors after curative‐intent resection for intrahepatic cholangiocarcinoma
Authors: Ma Zhi‐Jie , Xiang Jun‐Xi , Weiss Matthew , Popescu Irinel , Marques Hugo P. , Aldrighetti Luca , Maithel Shishir K. , Pulitano Carlo , Bauer Todd W. , Shen Feng , Poultsides George A. , Soubrane Oliver , Martel Guillaume , Koerkamp Bas Groot , Itaru Endo , Lyu Yi , Zhang Xu‐Feng , Pawlik Timothy M.
Published: June 2024

Objectives

The objective of the current study was to characterize prognostic factors related to long‐term recurrence‐free survival after curative‐intent resection of intrahepatic cholangiocarcinoma (ICC).

Methods

Data on patients who underwent curative‐intent resection for ICC between 2000 and 2020 were collected from an international multi‐institutional database. Prognostic factors were investigated among patients who recurred within 5 years versus long‐term survivors who survived more than 5 years with no recurrence.

Results

Among 635 patients who underwent curative‐intent resection for ICC, 104 (16.4%) patients were long‐term survivors with no recurrence beyond 5 years after surgery. Patients who survived for more than 5 years with no recurrence were more likely to have less aggressive tumor features, as well as have undergone an R0 resection versus patients who recurred within 5 years after resection. On multivariable analysis, tumor size (>5 cm) (HR: 1.535, 95% CI: 1.254–1.879), satellite lesions (HR: 1.253, 95% CI: 1.003–1.564), and lymph node metastasis (HR: 1.733, 95% CI: 1.349–2.227) were independently associated with recurrence within 5 years. Patients who recurred beyond 5 years (n = 23), 2–5 years (n = 60), and within 2 years (n = 471) had an incrementally worse post‐recurrence survival (PRS, 28.0 vs. 20.0 vs. 12.0 months, p = 0.032). Among patients with N0 status, tumor size (>5 cm) (HR: 1.612, 95% CI: 1.087–2.390) and perineural invasion (PNI) (HR: 1.562,95% CI: 1.081–2.255) were risk factors associated with recurrence. Among patients with N1 disease, only a minority (5/128, 3.9%) of patients survived with no recurrence to 5 years.

Conclusion

Roughly 1 in 6 patients survived for more than 5 years with no recurrence following curative‐intent resection of ICC. Among N0 patients, tumor recurrence was associated with tumor size and PNI. Only a small subset of N1 patients experienced long‐term survival.
Continuous chiral separation process for high‐speed countercurrent chromatography established and scaled up: A case of Voriconazole enantioseparation
Authors: Sun Xiao , Huang Xin‐Yi , Pei Dong , Di Duo‐Long
Published: June 2024

An efficient method for the continuous separation of Voriconazole enantiomers was developed using sulfobutyl ether‐β‐cyclodextrin (SBE‐β‐CD) as a chiral selector in high‐speed countercurrent chromatography (HSCCC) with different types. The separation was performed using a two‐phase solvent system consisting of n‐hexane/ethyl acetate/100 mmol/L phosphate buffer solution (pH = 3.0, containing 50 mmol/L SBE‐β‐CD) (1.5:0.5:2, v/v/v). A fast and predictable scale‐up process was achieved using an analytical DE HSCCC instrument. The optimized parameters were subsequently applied to a preparative Tauto HSCCC instrument, resulting in consistent separation time and enantiomeric purity, with throughput boosted by a remarkable 11‐fold. Preparative HSCCC successfully separated 506 mg of the racemate, delivering enantiomers exceeding 99% purity as confirmed by high‐performance liquid chromatography analysis. This investigation presents an effective methodology for forecasting the HSCCC scale‐up process and attaining continuous separation of chiral drugs.
Cutibacterium and Staphylococcus dysbiosis of the skin microbiome in acne and its decline after isotretinoin treatment
Authors: Feidenhansl Cecilie , Lund Michael , Poehlein Anja , Lood Rolf , Lomholt Hans B. , Brüggemann Holger
Published: June 2024

Background

Acne vulgaris is a multifactorial disease of the pilosebaceous unit of human skin. Previous studies have identified an acne‐associated dysbiosis of the skin microbiome.

Objectives

This dysbiosis was mainly determined for Cutibacterium acnes. However, detailed analyses combining qualitative and quantitative aspects are scarce, also regarding the possible contribution of other skin bacteria and the impact of treatment.

Methods

We conducted a culture‐independent study to determine differences between the healthy skin and the acne microbiome before and after isotretinoin treatment. Three amplicon‐based sequencing approaches and digital droplet PCR for quantification were applied.

Results

Our results revealed a 2.2‐fold reduced abundance of C. acnes with a reduced diversity in the acne microbiome. A phylotype switch was found, which was mainly characterized by a significant relative decrease of IB and II strains in the acne microbiome. In contrast, the relative abundance of staphylococci increased significantly and the quantitative ratio of staphylococci to C. acnes strongly increased from 1:34 in the healthy cohort to 1:11 in the acne cohort. The diversity of staphylococci was reduced, mainly due to the decrease of Staphylococcus hominis, and the appearance and predominance of Staphylococcus aureus in some acne patients. Isotretinoin treatment drastically depleted C. acnes (37‐fold) and moderately also staphylococci (3.6‐fold). Isotretinoin treatment resulted in a decrease of Staphylococcus epidermidis and a significant increase of S. aureus on facial skin.

Conclusions

The switch from a C. acnes‐dominated healthy skin microbiome towards an acne microbiome that is relatively enriched in staphylococci could indicate a stronger impact of staphylococci in the pathophysiology of acne than currently acknowledged. Our data further showed that isotretinoin largely eliminated the skin microbiome and in particular C. acnes, but also S. epidermidis. Instead, more harmful bacteria such as S. aureus could expand, suggesting that posttreatment strategies should be considered to accelerate skin microbiome recovery.
Correlating male white‐tailed deer antler size with female body mass across multiple spatial scales
Authors: Turner Mark A. , Harper Craig A. , Strickland Bronson K. , Lashley Marcus A. , Wilber Mark Q. , McKinley William
Published: June 2024

Managers use morphometric data collected from harvested animals as indicators of nutritional condition. Antler or horn size often are considered in ungulates, but there are problems associated with biased and limited harvest data available from male animals in many populations. Adult female body mass also may be collected, but little information exists on how male antler size scales with female body mass. We evaluated the relationship between property‐specific mature male white‐tailed deer (Odocoileus virginianus) antler size and adult female body mass from harvest data collected at 2 spatial scales. Regression predicted a 4.4‐cm increase in average mature male antler size for every 1‐kg increase in female body mass from 31 properties across the eastern United States, 2015–2023. Adult female mass explained 64% of the variation in mature antler size, and including latitude as a covariate did not improve model fit. When we considered data from 174 properties in Mississippi, USA, 1991–1994, we predicted a 4.7‐cm increase in average mature male antler size for every 1‐kg increase in adult female body mass. Including soil resource region in the Mississippi model explained 48% of the variation in mature male antler size by accounting for differences in average sizes across regions. Our results indicate average female body mass correlates with mature male antler size at multiple spatial scales. We recommend managers collect body mass and age from harvested female deer, as female mass represents a useful metric to track management progress and predict changes in antler size.
Knee braces and foot orthoses multimodal 3‐month treatment of medial knee osteoarthritis in a randomised crossover trial
Authors: Robert‐Lachaine Xavier , Dessery Yoann , Belzile Étienne L. , Corbeil Philippe
Published: June 2024

Purpose

Immediate biomechanical and functional benefits of knee braces and lateral wedge foot orthoses (FO) are often reported on patients with medial knee osteoarthritis. However, the effectiveness of their combined use in a longer‐term orthotic treatment remains unclear. The aim was to evaluate pain, function, comfort and knee adduction moment (KAM) during the stance phase of gait with three modalities of orthotic treatment.

Methods

Twenty‐two patients with knee osteoarthritis were analysed in a randomised crossover trial including a knee brace with valgus and external rotation functions (VER), FO and their combined use (VER + FO). Western Ontario and McMaster Universities scale (WOMAC) and Knee injury and Osteoarthritis Outcome Scores and KAM during gait were obtained before and after each orthotic treatment of 3 months. Repeated measures analyses of variance contrasted the factors orthosis (VER, FO, VER + FO), treatment (pre and post) and wear (without and with) on pain, function, comfort and KAM.

Results

An interaction between orthosis and treatment on the WOMAC pain (effect size [ES] = 0.17) and a main effect on the pain visual analogue score (ES = 0.24) indicated that VER and VER + FO were more alleviating than FO. The three modalities of orthotic treatment significantly improved functional scores (ES > 0.2) and reduced discomfort (ES = 0.25). A significant multivariate interaction between orthosis and wear (ES = 0.73) showed that the KAM reduction while wearing the orthoses was more pronounced with the VER and VER + FO than the FO.

Conclusion

The VER‐brace obtained more effectiveness than FO on pain and KAM after 3 months for medial knee osteoarthritis and the combined treatment did not substantially improve biomechanical and functional outcomes.

Level of Evidence

Therapeutic study level I randomised crossover trial.
The Transformation of Neck Unicentric Castleman's Disease to Follicular Dendritic Cell Sarcoma
Authors: Li Yingying , Shao Yue , Sun Xiumei , Huang Hai , Leng Xiaochen , Wang Yuliang
Published: June 2024

A patient with a large neck mass underwent appropriate imaging, routine blood tests, and serological evaluations. The medical history revealed the patient had undergone a lymphadenectomy in the same region 8 years ago, and the pathological diagnosis was the hyaline‐vascular subtype of unicentric Castleman's disease (UCD). The incisional biopsy and subsequent histopathological and immunohistochemical examination revealed the diagnosis of follicular dendritic cell sarcoma, consistent with the malignant transformation of UCD. UCD is uncommon and the malignant transformation of UCD is extremely rare in the head and neck region. Regional lymph node resection of one or more adjacent regions is the preferred treatment choice. Appropriate treatment procedures for UCD and regular follow‐up are essential for a good prognosis. Laryngoscope, 134:4985–4987, 2024
Fractional Radiofrequency and Oral Isotretinoin—A Prospective Randomized Controlled Split‐Face Trial Comparing Concurrent Versus Delayed Fractional Radiofrequency Treatment for Acne Scars
Authors: Gallo Elisa S. , Katz Uriel , Artzi Ofir
Published: June 2024

Background

Therapeutic dogma has been to treat acne scars no less than 6 months after isotretinoin (ITN) cessation.

Objective

To evaluate the safety and efficacy of fractional radiofrequency (FRF) in patients treated concurrently with ITN.

Methods

We conducted a prospective randomized control 3‐arm comparative trial to evaluate the treatment of acne scars. Patients received one of three treatment options: (A) ITN and FRF concurrent treatment, (B) ITN monotherapy, and (C) FRF 6 months post‐ITN treatment. Patients in the FRF cohorts received three monthly sessions. Patients were followed for adverse effects up to 6–9 months post‐FRF treatment. Final cosmesis was scored by three independent dermatologists using two scales: the Echelle d'Evaluation Clinique des Cicatrices d'Acne (ECCA) and an internal 5‐point investigator's scale, indicating the percentage of improvement. Subjective analyses by patients were also assessed.

Results

Objective and subjective analyses revealed improvement in the ITN‐FRF cohort, which was superior to the delayed FRF cohort and the ITN monotherapy cohort. Specifically, the concurrently treated cohort (ITN‐FRF) had a significant reduction in acne scar volume from baseline mean (151.1 ± 44.7 to 97.0 ± 31.2, p < 0.005), outperforming both the delayed FRF and monotherapy ITN treatment cohorts, respectively (155.4 ± 37.8 to 122.0 ± 46.2, 144.6 ± 82.8 to 132.4 ± 62.7). Additionally, the concurrently treated cohort demonstrated improved ECCA scores (36.8 ± 15.5), significantly better than the ITN monotherapy cohort (101.5 ± 20.1, p < 0.01).

Limitations

Limited patient sample size: 38 patients completed the study; mostly Fitzpatrick Type II–III skin; photographic assessments utilized.

Conclusion

Per our prospective trial, concurrent treatment of ITN‐FRF is superior to delayed FRF treatment 6 months post‐ITN cessation.
Evaluation of a Novel Ablative 1940 nm Pulsed Laser for Skin Rejuvenation
Authors: Gronovich Yoav , Raderman Yaniv , Toledano Ronen , Nahear Rotem , Suliman Neria , Shacham Alon , Friedman David J. , Noach Salman
Published: June 2024

Background

Skin rejuvenation is a widely sought‐after goal, prompting advancements in laser technology for noninvasive and effective treatments. Ablative lasers, in particular, have evolved to address diverse skin concerns, with fractional ablative lasers offering better‐tolerated outcomes. The introduction of a novel ablative Thulium pulsed laser, based on Thulium‐doped Yttrium aluminum Perovskite (Tm:YAP) crystal, delivers precise and controlled skin rejuvenation by allowing customization of ablative microcolumns.

Methods

A pilot in vivo study was conducted on the abdominal skin of a live female pig. Using the Laser Team Medical (LTM) prototype laser, treatments were administered with varying coagulation settings (minimal and maximum) and energies (32, 80, 120, and 160 mJ per microcolumn). Biopsies were harvested, fixed, and stained for subsequent analysis. The penetration depth and width of the microcolumns were evaluated.

Results

Low coagulation settings produced ablative microcolumns with thermal affected zones of 160 µm width, while high coagulation settings resulted in wider zones of 400–530 µm. The ablation cavities' width was estimated to be less than 100 µm in both settings. The novel 1940 nm pulsed laser demonstrated superior microcolumn properties, offering potential advantages such as shorter downtime and increased efficacy compared to existing fractional ablative lasers.

Conclusion

This study presents encouraging preliminary results regarding the efficacy and safety of the first ablative 1940 nm pulsed laser. The results show ablative microcolumns thinner than the counterpart devices, showing the device safety and potential higher efficacy along with short downtime. The LTM novel ablative 1940 nm pulsed laser holds immense potential for enhancing skin rejuvenation treatments due to its superior microcolumns properties. The versatility of this laser can open new treatment procedures and may extend to different areas of dermatology.
Smart Galactosidase‐Responsive Antimicrobial Dendron: Towards More Biocompatible Membrane‐Disruptive Agents
Authors: Shao Zeyu , Xu You Dan , Luo Hao , Hakobyan Karen , Zhang Mengnan , Xu Jiangtao , Stenzel Martina H. , Wong Edgar H. H.
Published: June 2024

Antimicrobial resistance is a global healthcare challenge that urgently needs the development of new therapeutic agents. Antimicrobial peptides and mimics thereof are promising candidates but mostly suffer from inherent toxicity issues due to the non‐selective binding of cationic groups with mammalian cells. To overcome this toxicity issue, this work herein reports the synthesis of a smart antimicrobial dendron with masked cationic groups (Gal‐Dendron) that could be uncaged in the presence of β‐galactosidase enzyme to form the activated Enz‐Dendron and confer antimicrobial activity. Enz‐Dendron show bacteriostatic activity toward Gram‐negative (P. aeruginosa and E. coli) and Gram‐positive (S. aureus) bacteria with minimum inhibitory concentration values of 96 µm and exerted its antimicrobial mechanism via a membrane disruption pathway, as indicated by inner and outer membrane permeabilization assays. Crucially, toxicity studies confirmed that the masked prodrug Gal‐Dendron exhibited low hemolysis and is at least 2.4 times less toxic than the uncaged cationic Enz‐Dendron, thus demonstrating the advantage of masking the cationic groups with responsive immolative linkers to overcome toxicity and selectivity issues. Overall, this study highlights the potential of designing new membrane‐disruptive antimicrobial agents that are more biocompatible via the amine uncaging strategy.
ZBTB7A interferes with the RPL5‐P53 feedback loop and reduces endoplasmic reticulum stress‐induced apoptosis of pancreatic cancer cells
Authors: Tang Jie , Chen Lingling , Chang Yunli , Hang Dongyun , Chen Guoyu , Wang Ying , Feng Lingmei , Xu Ming
Published: June 2024

Endoplasmic reticulum (ER) stress is a primary mechanism leading to cell apoptosis, making it of great research interests in cancer management. This study delves into the function of ribosomal protein L5 (RPL5) in ER stress within pancreatic cancer (PCa) cells and investigates its regulatory mechanisms. Bioinformatics predictions pinpointed RPL5 as an ER stress‐related gene exhibiting diminished expression in PCa. Indeed, RPL5 was found to be poorly expressed in PCa tissues and cells, with this reduced expression correlating with an unfavorable prognosis. Moreover, RPL5 overexpression led to heightened levels of p‐PERK, p‐eIF2α, and CHOP, bolstering the proapoptotic effect of Tunicamycin, an ER stress activator, on PCa cells. Additionally, the RPL5 overexpression curbed cell proliferation, migration, and invasion. Tunicamycin enhanced the binding between RPL5 and murine double minute 2 (MDM2), thus suppressing MDM2‐mediated ubiquitination and degradation of P53. Consequently, P53 augmentation intensified ER stress, which further enhanced the binding between RPL5 and MDM2 through PERK‐dependent eIF2α phosphorylation, thereby establishing a positive feedback loop. Zinc finger and BTB domain containing 7A (ZBTB7A), conspicuously overexpressed in PCa samples, repressed RPL5 transcription, thereby reducing P53 expression. Silencing of ZBTB7A heightened ER stress and subdued the malignant attributes of PCa cells, effects counteracted upon RPL5 silencing. Analogous outcomes were recapitulated in vivo employing a xenograft tumor mouse model, where ZBTB7A silencing dampened the tumorigenic potential of PCa cells, an effect reversed by additional RPL5 silencing. In conclusion, this study suggests that ZBTB7A represses RPL5 transcription, thus impeding the RPL5‐P53 feedback loop and mitigating ER‐induced apoptosis in PCa cells.
Targeting RNA‐binding motif protein 39 for arginine reduction: unveiling metabolic vulnerability in arginine‐dependent liver cancer
Authors: Li Aoxue , Cui Hongjuan , Zhao Erhu
Published: June 2024

Cancer is increasingly acknowledged as a metabolic disease, characterized by metabolic reprogramming as its hallmark. However, the precise mechanisms behind this phenomenon and the factors contributing to tumorigenicity are still poorly understood. In a recent publication in Cell, Mossmann and colleague reported a study unveiling arginine as a molecule with second messenger‐like properties that reshapes metabolism to facilitate the tumor development in hepatocellular carcinoma (HCC). Their research revealed that the RNA‐binding motif protein 39 (RBM39)‐mediated increase in asparagine synthesis results in increased arginine uptake. This establishes a positive feedback loop that sustains elevated levels of arginine and facilitates oncogenic metabolic reprogramming. Additionally, Mossmann et al. demonstrated that depleting RBM39 with indisulam effectively disrupts the proto‐oncogenic metabolic reprogramming in HCC. This discovery presents a novel treatment strategy for arginine‐dependent liver cancers.
No evidence of Fabry disease in a patient with the new p.Met70Val GLA gene variant
Authors: Capelli Irene , Di Costanzo Roberta , Aiello Valeria , Lerario Sarah , De Giovanni Paola , Montevecchi Marcello , Cerretani Davide , Donadio Vincenzo , La Manna Gaetano , Mignani Renzo
Published: June 2024

Background

Fabry disease (FD) is a rare X‐linked lysosomal storage disorder caused by variants in GLA gene leading to deficient α‐galactosidase A enzyme activity. This deficiency leads to the accumulation of glycosphingolipids, particularly globotriaosylceramide (Gb3), in various tissues and organs, which can result in life‐threatening complications. The clinical presentation of the disease can vary from the “classic” phenotype with pediatric onset and multi‐organ involvement to the “later‐onset” phenotype, which presents with predominantly cardiac symptoms. In recent years, advances in screening studies have led to the identification of an increasing number of variants of unknown significance that have not yet been described, and whose pathogenic role remains undetermined.

Methods

In this clinical report, we describe the case of an asymptomatic adult female who was found to have a new variant of unknown significance, p.Met70Val. Given the unknown pathogenic role of this variant, a thorough analysis of the potential organ involvement was conducted. The clinical data were analyzed retrospectively.

Results

The analysis revealed that there were no signs of significant organ involvement, and the benignity of the variant was confirmed.

Conclusion

This case underscores the importance of a comprehensive evaluation of new variants of unknown significance to establish their pathogenicity accurately.
Error estimate of GL‐ADI scheme for 2D multiterm nonlinear time‐fractional subdiffusion equation
Authors: Jiang Yubing , Chen Hu
Published: June 2024

In this paper, a 2D multiterm nonlinear problem of the form
is considered, where each Caputo fractional derivative is of order
. We use the Grünwald–Letnikov(GL) scheme on uniform mesh to discretize the multiterm Caputo fractional derivative and finite difference scheme is used for spatial discretization, and then we construct a fully discrete GL‐ADI scheme. A discrete Gronwall inequality is introduced for getting the sharp pointwise‐in‐time error estimate on uniform mesh. Numerical examples are provided to verify the sharpness of our error estimate.
Ultrafast T2 and T2* mapping using single‐shot spatiotemporally encoded MRI with reduced field of view and spiral out‐in‐out‐in trajectory
Authors: Jin Junxian , Zhou Yang , Chen Lin , Chen Zhong
Published: June 2024

Background

T2 and T2* mapping are crucial components of quantitative magnetic resonance imaging, offering valuable insights into tissue characteristics and pathology. Single‐shot methods can achieve ultrafast T2 or T2* mapping by acquiring multiple readout echo trains. However, the extended echo trains pose challenges, such as compromised image quality and diminished quantification accuracy.

Purpose

In this study, we develop a single‐shot method for ultrafast T2 and T2* mapping with reduced echo train length.

Methods

The proposed method is based on ultrafast single‐shot spatiotemporally encoded (SPEN) MRI combined with reduced field of view (FOV) and spiral out‐in‐out‐in (OIOI) trajectory. Specifically, a biaxial SPEN excitation scheme was employed to excite the spin signal into the spatiotemporal encoding domain. The OIOI trajectory with high acquisition efficiency was employed to acquire signals within targeted reduced FOV. Through non‐Cartesian super‐resolved (SR) reconstruction, 12 aliasing‐free images with different echo times were obtained within 150 ms. These images were subsequently fitted to generate T2 or T2* mapping simultaneously using a derived model.

Results

Accurate and co‐registered T2 and T2* maps were generated, closely resembling the reference maps. Numerical simulations demonstrated substantial consistency (R2 > 0.99) with the ground truth values. A mean difference of 0.6% and 1.7% was observed in T2 and T2*, respectively, in in vivo rat brain experiments compared to the reference. Moreover, the proposed method successfully obtained T2 and T2* mappings of rat kidney in free‐breathing mode, demonstrating its superiority over multishot methods lacking respiratory navigation.

Conclusions

The results suggest that the proposed method can achieve ultrafast and accurate T2 and T2* mapping, potentially facilitating the application of T2 and T2* mapping in scenarios requiring high temporal resolution.