bluuebunny/crossref_metadata_2025_split huggingface dataset:
T Cell–Mediated Targeted Delivery of Anti–PD-L1 Nanobody Overcomes Poor Antibody Penetration and Improves PD-L1 Blocking at the Tumor Site
Authors: Petit Pierre-Florent , Bombart Raphaële , Desimpel Pierre-Hubert , Naulaerts Stefan , Thouvenel Laurie , Collet Jean-François , Van den Eynde Benoit J. , Zhu Jingjing 
Published: April 2022

Abstract

Monoclonal antibodies (mAbs) blocking immune checkpoints such as programmed death ligand 1 (PD-L1) have yielded strong clinical benefits in many cancer types. Still, the current limitations are the lack of clinical response in a majority of patients and the development of immune-related adverse events in some. As an alternative to PD-L1–specific antibody injection, we have developed an approach based on the engineering of tumor-targeting T cells to deliver intratumorally an anti–PD-L1 nanobody. In the MC38-OVA model, our strategy enhanced tumor control as compared with injection of PD-L1–specific antibody combined with adoptive transfer of tumor-targeting T cells. As a possible explanation for this, we demonstrated that PD-L1–specific antibody massively occupied PD-L1 in the periphery but failed to penetrate to PD-L1–expressing cells at the tumor site. In sharp contrast, locally delivered anti–PD-L1 nanobody improved PD-L1 blocking at the tumor site while avoiding systemic exposure. Our approach appears promising to overcome the limitations of immunotherapy based on PD-L1–specific antibodies.
The RAISE Trial: A Novel Device and First-in-Man Trial
Authors: Sun Wei , Zou Huayiyang , Yong Yonghong , Liu Boxun , Zhang Hao , Lu Jieyu , Shen Yihui , Li Peng , Xu Tianhua , Chen Xuguan , Du Anning , Jiang Ming , Hua Yang , Sheng Yanhui , Zhou Bin , Lotan Chaim , Kong Xiangqing 
Published: April 2022

Background:
Currently, standard medical therapies have limited effects on heart failure with preserved ejection fraction (HFpEF), which impacts on the life quality and survival of patients. This study aimed to evaluate the safety and efficacy of the percutaneous radiofrequency ablation–based interatrial shunting for HFpEF with a novel atrial septostomy device.

Methods:
A preclinical study in 11 normal domestic pigs and the first-in-man study in 10 patients with HFpEF were performed. The major safety events and interatrial shunt performance were evaluated at baseline, 1 month, 3 months, and 6 months post-procedure in both animals and human patients. The clinical functional status was also assessed in the first-in-man study.

Results:

Percutaneous radiofrequency ablation–based interatrial shunting therapy was performed successfully both in animals and patients. In the animal study, a left-to-right interatrial shunt was created with a mean defect size of 5.5±2.2 mm without procedure-related safety events. Seven pigs showed the continuous shunting with a mean defect size of 4.1±1.5 mm at 6 months. In the first-in-man study, a median interatrial defect diameter of 5.0 (4.0–6.0) mm was measured immediately. No major safety events including death and thromboembolism were observed. The continuous shunting with the defect size of 4.0 (3.0–4.0) mm could still be observed in 7 patients at 6 months. The clinical status was significantly improved with NT-proBNP (N-terminal pro-B-type natriuretic peptide) reduced by 2149 pg/mL ([95% CI, 204–3301]
P
=0.028), with 6-minute walk distance increased by 88 m ([95% CI, 50–249]
P
=0.008) and with New York Heart Association class improved in 8 patients at 6 months.

Conclusions:
The present results showed that percutaneous radiofrequency ablation–based interatrial shunting was a safe and potentially effective therapy for HFpEF, providing a nonpharmacological and nonimplanted option for HFpEF management.

Registration:

URL:
https://www.chictr.org.cn
; Unique identifier: ChiCTR1900027664.
Progressive Reduction in Right Ventricular Contractile Function Attributable to Altered Actin Expression in an Aging Mouse Model of Arrhythmogenic Cardiomyopathy
Authors: Camors Emmanuel M. , Roth Alyson H. , Alef Joseph R. , Sullivan Ryan D. , Johnson Jason N. , Purevjav Enkhsaikhan , Towbin Jeffrey A. 
Published: April 2022

Background:

Arrhythmogenic cardiomyopathy (ACM) is an inherited genetic disorder of desmosomal dysfunction, and PKP2 (plakophilin-2) has been reported to be the most common disease-causing gene when mutation-positive. In the early concealed phase, the ACM heart is at high risk of sudden cardiac death before cardiac remodeling occurs because of mistargeted ion channels and altered Ca
2+
handling. However, the results of pathogenic PKP2 variants on myocyte contraction in ACM pathogenesis remain unknown.

Methods:

We studied the outcomes of a human truncating variant of PKP2 on myocyte contraction using a novel knock-in mouse model with insertion of thymidine in exon 5 of
Pkp2
, which mimics a familial case of ACM (PKP2-L404fsX5). We used serial echocardiography, electrocardiography, blood pressure measurements, histology, cardiomyocyte contraction, intracellular calcium measurements, and gene and protein expression studies.

Results:

Serial echocardiography of Pkp2 heterozygous (Pkp2-Het) mice revealed progressive failure of the right ventricle (RV) in animals older than 3 months. By contrast, left ventricular function remained normal. ECGs of 6-month-old anesthetized Pkp2-Het mice showed normal baseline heart rates and QRS complexes. Cardiac responses to β-adrenergic agonist isoproterenol (2 mg/kg) plus caffeine (120 mg/kg) were also normal. However, adrenergic stimulation enhanced the susceptibility of Pkp2-Het hearts to tachyarrhythmia and sudden cardiac death. Histological staining showed no significant fibrosis or adipocyte infiltration in the RVs and left ventricles of 6- and 12-month-old Pkp2-Het hearts. Contractility assessment of isolated myocytes demonstrated progressively reduced Pkp2-Het RV cardiomyocyte function consistent with RV failure measured by echocardiography. However, aging Pkp2-Het and control RV myocytes loaded with intracellular Ca
2+
indicator Fura-2 showed comparable Ca
2+
transients. Western blotting of Pkp2-RV homogenates revealed a 40% decrease in actin, whereas actin immunoprecipitation followed by a 2,4-dinitrophenylhydrazine staining showed doubled oxidation level. This correlated with a 39% increase in troponin-I phosphorylation. In contrast, Pkp2-Het left ventricular myocytes had normal contraction, actin expression and oxidation, and troponin-I phosphorylation. Last, Western blotting of cardiac biopsies revealed that actin expression was 40% decreased in RVs of patients with end-stage ACM.

Conclusions:
During the early concealed phase of ACM, reduced actin expression drives loss of RV myocyte contraction, contributing to progressive RV dysfunction.
A new species of Apisa Walker, 1855 (Lepidoptera: Erebidae: Arctiinae) from Uganda with remarks on the apomorphies of the genus
Authors: PRZYSTAŁKOWSKA ANNA 
Published: April 2022

A new species of Apisa Walker, 1855 from Uganda (East Africa) and Gabon (Central Africa) is described according to morphological characters and DNA barcode information. A diagnosis, detailed description, distribution, and illustrations of specimens and the male genitalia are provided. Diagnostic characters are found in wing shape, strongly marked wing venation and details of the male genital apparatus.
The DNA barcode sequences of twelve specimens of A. atrovenosa sp. n. are compared with other members of Apisa. Diagnostic characters of the genus are summarised and discussed for the first time with an emphasis on the lack of arolium as the obvious autapomorphy. This character is shown by SEM photographs.
A Three-Dimensional Finite Element Analysis of Mini-Implant supported K-Loop for Maxillary Molar Distalization
Authors: Tekale Pawankumar Dnyandeo , Patil Harshal Ashok , Garg Kamlesh , Kerudi Veerendra V. , Parhad Sameer M , Sharan Jitendra S. , Lohakpure Ratnadip A. , Raina Sakshi 
Published: April 2022

Introduction: The study was conducted to assess the stress and displacement effects of a mini-implant supported k-loop on the maxillary dentition for distalization with 3-dimensional (3D) finite element stress analysis. Materials and Methods: A 3D model of the maxilla with all teeth, periodontal ligament, bone, mini-implants, brackets, and archwire was used in this study. The analytic model used in this study like brackets, wire, K-loop, and mini-implants was developed using a reverse engineering technique extracting the dimensional details of the physical parts using precision measuring instruments. Results: The distobuccal movement on the first molar and second molar were 0.26864 mm and 0.00833 mm, respectively. A total of 0.25 mm intrusion movement was seen on distal cusp of the first molar and 0.14 mm extrusion movement seen on mesial cusp of the first molar. A total of 0.25 mm and 0.00260 mm intrusion movement was seen on the distal cusp of the first molar and second molar, respectively. A total of 0.14 mm and 0.00324 mm extrusion movement was seen on the mesial cusp of the first molar and second molar, respectively. Conclusions: There was a large amount of distal displacement of the first molar, also negligible amount of tipping of the first molar and mesial movement of first premolar.
The Effect of Patellar Surface Morphology on Subchondral Bone Alignment When Matching Patellar Osteochondral Allografts to the Central Ridge of the Patella
Authors: Neral Mithun , Patel Karan A. , Getty Michael , Salka Nabeel , Grant John A. 
Published: April 2022

Background: Cartilage transplants in the patellofemoral joint have demonstrated lower success rates than in the femoral condyles. This is likely related to the more complex morphology and biomechanics of the joint. While previous studies have evaluated cartilage surface matching and congruence, little work has been done to study the associated subchondral bone congruency in these grafts. Purpose: To determine if differences in patellar morphology play a role in the alignment of the donor patellar osteochondral allograft subchondral bone with the native patellar subchondral bone. Study Design: Controlled laboratory study. Methods: A total of 20 (10 Wiberg I and 10 Wiberg II/III) fresh-frozen human patellae were designated as recipients and size-matched to both a Wiberg I and a Wiberg II/III patellar donor. A 16-mm osteochondral allograft transplant to the central ridge of the patella was performed in random order with each matched donor. Transplanted patellae underwent a nano—computed tomography (nano-CT) scan, were digitally reconstructed, and were superimposed on the initial nano-CT scan of the native recipient patella. MATLAB was used to determine the surface height deviation between the native and donor subchondral bone surfaces. DragonFly 3-dimensional imaging software was used to measure subchondral bone step-off heights at the native-donor interface. Differences between matched and unmatched grafts were compared using a 2-way analysis of variance and the Sidak post hoc test. Results: Subchondral bone surface deviation did not differ between Wiberg matched and unmatched allografts. The step-off height was significantly greater in unmatched (1.38 ± 0.49 mm) compared with matched (1.14 ± 0.52 mm) plugs ( P = .015). The lateral quadrant step-off differed between matched (0.89 ± 0.43 mm) and unmatched (1.60 ± 0.78 mm) grafts ( P = .007). Conclusion: While unmatched Wiberg patellar osteochondral allograft implantation did not result in significantly different subchondral bone surface height deviations, there was a significant difference in the circumferential subchondral bone step-off height in the lateral quadrant. Further investigation using finite element analysis modeling will help determine the role of subchondral bone surface on shear and compression force distributions in these areas. Clinical Relevance: Given that subchondral bone stiffness and morphology play a role in cartilage health, subchondral bone congruency may play a role in graft survival. Understanding how this congruency plays a role in cartilage force distribution will help surgeons improve the long-term success of osteochondral allograft transplants.
Dual-mobility constructs versus large femoral head bearings in primary and revision total hip arthroplasty: a systematic review and meta-analysis of comparative studies
Authors: Hoskins Wayne , McDonald Laura , Claireaux Harry , Bingham Roger , Griffin Xavier 
Published: April 2022

Background: Both dual-mobility (DM) constructs and large femoral head bearings (⩾36 mm) reduce dislocation following total hip arthroplasty (THA). There is limited research comparing DM with large bearings. Methods: A systematic review of published literature was performed including studies that compared DM with large femoral head bearings in primary or revision THA according to PRISMA guidelines. The primary outcome was revision surgery for dislocation. The secondary outcome was all-cause revision surgery. Other complications were recorded. 2 authors independently selected studies, performed data extraction, and risk of bias assessment. Treatment effects were assessed using odds ratios and data were pooled using a fixed-effect model, where appropriate. Results: 9 studies, all retrospective, met the final inclusion criteria. 2722 patients received DM and 9,789 large femoral head bearings. The difference in the odds of revision surgery for dislocation (OR 0.67; 95% CI, 0.45–1.01; p = 0.06) and aseptic loosening are unclear (OR 0.61; 95% CI, 0.36–1.05; p = 0.07); including important benefits and no difference. There was a benefit favouring DM for the risk of all-cause revision (OR 0.70; 95% CI, 0.56–0.86; p = 0.001), revision for fracture (OR 0.49; 95% CI, 0.29–0.81; p = 0.005) and dislocation not requiring revision (OR 0.29; 95% CI, 0.14–0.57; p < 0.001). The estimate in the difference in the odds of revision surgery for infection was imprecise (OR 0.78; 95% CI, 05.1–1.20; p = 0.26). Conclusions: This study provides evidence that there may be clinically relevant benefits of DM constructs over large femoral head bearings. Prospective randomised studies are warranted given these findings.
Earlier functional recovery and discharge from hospital for THA patients operated on via direct superior compared to standard posterior approach: a retrospective frequency-matched case-control study
Authors: Kenanidis Eustathios , Paparoidamis George , Pegios Vasileios F , Anagnostis Panagiotis , Potoupnis Michael , Tsiridis Eleftherios 
Published: April 2022

Background: The direct superior hip approach (DSA) has been less researched than other approaches in the literature. We retrospectively compared the early postoperative and functional outcomes of patients with hip osteoarthritis undergoing total hip arthroplasty (THA) via DSA with a matched control group using a standard posterior approach (SPA). Methods: The DSA group comprised 100 THAs performed via DSA by a senior surgeon between January 2018 and May 2019. Patients with primary osteoarthritis and ASA score ⩽3 who were eligible for surgery were included. The DSA group was compared to a matched cohort of 100 patients operated on with a SPA in the same period by another chief surgeon. Patients were matched for age, sex, and ASA score. All patients received the same postoperative chemoprophylaxis, pain management and physiotherapy. 2 independent attending arthroplasty surgeons assessed the incision length, operative time, blood loss, hospital stay, and complications. VAS, HHS, and HOOS scores were also evaluated for a year postoperatively. Results: Mean incision length and hospital stay were significantly lower in the DSA group. DSA patients had non-significantly lower intraoperative blood loss, transfusion needs, and postoperative pain than SPA patients. Mean operation time and complication rate did not differ between groups. The DSA group demonstrated significantly greater functional scores than the SPA group at the first postoperative month. No differences in scores were recorded following the third month. Conclusions: The DSA approach may provide earlier functional recovery and hospital discharge for THA patients compared with SPA. DSA was equivalent to SPA concerning pain and blood loss, showing minimal complication rates.
COVID-19 Infections in Cancer Patients Were Frequently Asymptomatic: Description From a French Prospective Multicenter Cohort (PAPESCO-19)
Authors: Zhou Ke , Raoul Jean-Luc , Blanc-Lapierre Audrey , Seegers Valérie , Boisdron-Celle Michèle , Bourdon Marianne , Mahammedi Hakim , Lambert Aurélien , Moreau-Bachelard Camille , Campone Mario , Conroy Thierry , Penault-Llorca Frédérique , Bellanger Martine M , Bigot Frédéric 
Published: April 2022

Background: Cancer patients (CPs) are considered more vulnerable and as a high mortality group regarding COVID-19. In this analysis, we aimed to describe asymptomatic COVID (+) CPs and associated factors. Methods: We conducted a prospective study in CPs and health care workers (HCWs) in 4 French cancer centers (PAPESCO [ PAtients et PErsonnels de Santé des Centres de Lutte Contre le Cancer pendant l’épidémie de COvid-19] study). This analysis used data recorded between June 17, 2020 and November 30, 2020 in CPs (first 2 waves, no variants). At inclusion and quarterly, CPs reported the presence of predefined COVID-19 symptoms and had a blood rapid diagnostic test; a reverse transcription polymerase chain reaction (RT-PCR) was done in case of suspected infection. Results: A total 878 CPs were included; COVID-19 prevalence was similar in both CPs (8%) and HCWs (9.5%); of the 70 CPs (8%) who were COVID (+), 29 (41.4%) were and remained asymptomatic; 241/808 of the COVID (−) (29.8%) were symptomatic. 18 COVID (+) were hospitalized (2% of CPs), 1 in intensive care unit (ICU) and 1 died (0.1% of CPs and 2.4% of symptomatic COVID [+] CPs). Only the inclusion center was associated with clinical presentation (in Nancy, Angers, Nantes, and Clermont-Ferrand: 65.4%, 35%, 28.6%, and 10% CPs were asymptomatic, respectively). Conclusions: Seroprevalence of COVID-19 in CPs was similar to that observed in HCWs; mortality related to COVID-19 among CPs was 0.1%. More than 40% of COVID (+) CPs were asymptomatic and one third of COVID (−) CPs had symptoms. Only geographic origin was associated with the presence or absence of symptoms. Social distancing and protective measures must be applied in CPs at home and when hospitalized.
Experience of UK Latin Americans caring for a relative living with dementia: A qualitative study of family carers
Authors: Guerra Stefanny , James Tiffeny , Rapaport Penny , Livingston Gill 
Published: April 2022

Introduction Most studies of the Latin American immigrant experience and care for relatives living with dementia have been in the United States (US). In the United Kingdom (UK), unlike the US, most Latin Americans are first generation immigrants and are a rapidly increasing population. Therefore, we aimed to explore the UK experiences of Latin Americans caring for a relative with dementia. Methods We purposively recruited UK-based Latin American family carers of people with dementia ensuring maximum diversity. We conducted semi-structured qualitative interviews (in English or Spanish) with 11 family carers, stopping recruiting when we reached thematic saturation. We took an inductive thematic analytic approach. Findings Four main themes were identified: (1) Family comes first, particularly older people, leading to an obligation to care; (2) dementia as an illness that is accepted and talked about, which is regarded as positive with close networks but not wider society; (3) difficult behaviours are not the responsibility of the person with dementia, who is often conceptualised as a child; and (4) caring expectations lead to incompatibility with formal services, and a reluctance to leave people with dementia alone. Conclusions Familial obligation is the driver for family carers and acceptance of the illness helped despite adversities. Openness to talk about dementia with close networks was distinctive and helpful, contrasting with wider society, where greater awareness of dementia is needed. Considering the person with dementia as a child did not seem to undermine personhood and enabled maintenance of compassion. The relative with dementia was a priority. There was a lack of culturally and linguistically appropriate services, thus restricting family carers’ ability to fulfil other roles, such as parental.
Sage seed gum as a novel source for polysaccharide-based antibacterial nanofibers: Physical, chemical, and rheological characterization
Authors: Yekrang Javad , Saghafi Reza , Yousefi Alireza , Ghaffari Fatemeh 
Published: April 2022

In this study, the sage seed gum (SSG) was electrospun as a polysaccharide polymer blended with polyvinyl alcohol (PVA) to construct nanofibrous mats for antibacterial applications. The rheological properties of the PVA/SSG solutions were investigated before electrospinning. Oscillatory, shear, and steady shear tests demonstrated that the PVA/SSG solutions had a viscous behavior, exhibiting a higher consistency coefficient ( k) and a lower flow behavior index ( n) at the higher PVA incorporation levels. The morphological studies by SEM images revealed that the PVA/SSG nanofibers were produced without bead defects within the diameter range of 130–300 nm. The in vitro degradation tests showed that the PVA/SSG nanofibers (at different SSG contents) were degraded by approx. 60–70% of their initial weight after one day of the degradation test. The antibacterial activity against Escherichia coli and Staphylococcus aureus microbial species and biodegradation tests also verified that the produced nanofibers could be implemented for antibacterial applications. The SSG polymer in the form of nanofibers can be, therefore, used as a natural and low-cost polymer for special antibacterial applications such as wound healing.
Association of prostate size with capsule thickness and glandular epithelial cell density: The possible clinical implications on prostate cancer development
Authors: Sellers Jake , Ward Ellen , Weaver Preston , Garza John , Brandi Luis , de Riese Werner TW 
Published: April 2022

Objective: Benign prostatic hyperplasia (BPH) and prostate cancer (PCa) are the two most common urologic diseases in aging males. The negative association between prostate/BPH size and incidence of PCa is well documented in the literature. However, the exact mechanism is not well understood. This study aims to further investigate the possible effect of prostate volume on prostate capsule thickness and glandular cell density in the prostatic peripheral zone (PZ). Materials and Methods: A total of 100 patients were selected that had undergone radical prostatectomy with prostate sizes ranging from 20 to 160 mL. Quantitative measurements of capsule thickness and density of epithelial glands within the peripheral zone not affected by cancer were analysed and calculated on histo-anatomical slides using computer-based imaging software. Associations between the different variables were calculated using Spearman correlation with 95% confidence intervals (CIs). Results: In the non-cancerous areas of the PZ, prostate volume and average capsule thickness are positively associated ( rs = +0.6526, 95% CI +0.5233 to +0.7526, p < 0.0001), while prostate volume and average glandular epithelial cell density of the PZ are negatively associated ( rs = −0.6011, 95% CI −0.7133 to −0.4589, p < 0.0001). These associations remain consistent on subgroup analysis. Conclusion: The findings of this study support the hypothesis that transition zone (TZ) growth in large BPH prostates may cause pressure on the outer PZ, leading to fibrosis and atrophy of the glandular tissue. This may provide a protective effect against PCa, as most PCa originates in the PZ of the prostate. Level of evidence: Not applicable