bluuebunny/crossref_metadata_2025_split huggingface dataset:
Engineering nano-drug biointerface to overcome biological barriers toward precision drug delivery
Authors: Waheed Saquib , Li Zhibin , Zhang Fangyingnan , Chiarini Anna , Armato Ubaldo , Wu Jun 
Published: August 2022

AbstractThe rapid advancement of nanomedicine and nanoparticle (NP) materials presents novel solutions potentially capable of revolutionizing health care by improving efficacy, bioavailability, drug targeting, and safety. NPs are intriguing when considering medical applications because of their essential and unique qualities, including a significantly higher surface to mass ratio, quantum properties, and the potential to adsorb and transport drugs and other compounds. However, NPs must overcome or navigate several biological barriers of the human body to successfully deliver drugs at precise locations. Engineering the drug carrier biointerface can help overcome the main biological barriers and optimize the drug delivery in a more personalized manner. This review discusses the significant heterogeneous biological delivery barriers and how biointerface engineering can promote drug carriers to prevail over hurdles and navigate in a more personalized manner, thus ushering in the era of Precision Medicine. We also summarize the nanomedicines' current advantages and disadvantages in drug administration, from natural/synthetic sources to clinical applications. Additionally, we explore the innovative NP designs used in both non-personalized and customized applications as well as how they can attain a precise therapeutic strategy.
Identification and ultrasensitive photoelectrochemical detection of LncNR_040117: a biomarker of recurrent miscarriage and antiphospholipid antibody syndrome in platelet-derived microparticles
Authors: Sun Zhiwei , Zhou Qian , Yang Yufei , Li Lei , Yu Mengru , Li Hui , Li Aihua , Wang Xietong , Jiang Yanyan 
Published: August 2022

AbstractThe abnormal expression of long non-coding RNAs (LncRNAs) in platelet-derived microparticles (PMPs) is closely related to immune disorders and may lead to antiphospholipid antibody syndrome and recurrent miscarriage. To understand the association between the LncRNAs in PMPs and RM/APS, the differences in the expression of LncRNAs in RM/APS patients and healthy controls were analyzed. Microarray analysis and RT-qPCR detection proved that RM/APS patient exhibited high levels of LncNR_040117 expression. The lentiviral silent expression transfection of HTR-8/SVneo cells indicated that LncNR_040117 downregulation decreased the activity of HTR-8/SVneo cells and inhibited the MAPK signaling pathway, further confirming the biomarker proficiency of LncNR_040117 for RM/APS. After that, we proposed a β-In2S3@g-C3N4nanoheterojunction-based photoelectrochemical (PEC) biosensor to achieve the ultrasensitive detection of LncNR_040117. The nanoheterojunction aids in the effective separation of photogenerated carriers and significantly improve the photocurrent response of the biosensor. The conjugation of LncNR_040117 onto the PEC biosensing platform increased the steric hindrance between electrolyte and electrode, subsequently decreasing the photocurrent signal. The PEC biosensor showed a wide detection range of 0.1–106fM and a low limit of detection of 0.025 fM. For clinical sample testing, the results of the PEC and RT-qPCR were highly consistent. Overall, LncNR_040117 in PMPs was identified as an effective biomarker for RM/APS and could be accurately detected by the proposed PEC biosensor, which is expected to provide a reliable diagnostic platform for RM/APS.
Hyperlipidemia does not influence clinical outcome in arthroscopic treatment of femoroacetabular impingement syndrome
Authors: Yang Fan , Huang Hong-Jie , Zhang Zhu , Zhang Xin , Wang Jian-Quan 
Published: August 2022

Abstract
Background
Cholesterol can trigger degenerative processes in the chondrocytes. The internal layer of the hip labral consists of cartilage-specific type II collagen-positive fibrocartilage. The purpose of this study was to compare outcomes after arthroscopy labral repair in FAIS patients with preoperative hyperlipidemia to a control group with no hyperlipidemia.

Methods
Data were prospectively collected and retrospectively reviewed for FAIS patients who had arthroscopy 2019. Patients with hyperlipidemia were 1:1 propensity-score matched to patients without hyperlipidemia. Patient-reported outcomes (HOS-ADL, iHOT-12, mHHS), VAS scores, radiographic measures, performed procedures, complications, and revision surgery were compared and analyzed for both groups.

Results
A total of 41 patients with hyperlipidemia and 41 patients without hyperlipidemia were found using propensity-score matching. When compared to preoperative levels, both groups demonstrated significant improvements in PROs and VAS scores at the final follow-up. Besides, there were no significant differences in preoperative scores and final outcome scores between the groups. Besides, there were no other differences in revision rate and the rate of meeting the PASS and MCID between the study and the control groups.

Conclusion
It was demonstrated in this study that FAIS patients with hyperlipidemia can expect to experience similar good short-term patient-reported outcomes as compared with patients without hyperlipidemia.

Level of evidence
Case-series study; Level of Evidence: Level III.
Genome-wide interrogation of structural variation reveals novel African-specific prostate cancer oncogenic drivers
Authors: Gong Tingting , Jaratlerdsiri Weerachai , Jiang Jue , Willet Cali , Chew Tracy , Patrick Sean M. , Lyons Ruth J. , Haynes Anne-Maree , Pasqualim Gabriela , Brum Ilma Simoni , Stricker Phillip D. , Mutambirwa Shingai B. A. , Sadsad Rosemarie , Papenfuss Anthony T. , Bornman Riana M. S. , Chan Eva K. F. , Hayes Vanessa M. 
Published: August 2022

AbstractBackgroundAfrican ancestry is a significant risk factor for advanced prostate cancer (PCa). Mortality rates in sub-Saharan Africa are 2.5-fold greater than global averages. However, the region has largely been excluded from the benefits of whole genome interrogation studies. Additionally, while structural variation (SV) is highly prevalent, PCa genomic studies are still biased towards small variant interrogation.MethodsUsing whole genome sequencing and best practice workflows, we performed a comprehensive analysis of SVs for 180 (predominantly Gleason score ≥ 8) prostate tumours derived from 115 African, 61 European and four ancestrally admixed patients. We investigated the landscape and relationship of somatic SVs in driving ethnic disparity (AfricanversusEuropean), with a focus on African men from southern Africa.ResultsDuplication events showed the greatest ethnic disparity, with a 1.6- (relative frequency) to 2.5-fold (count) increase in African-derived tumours. Furthermore, we found duplication events to be associated withCDK12inactivation andMYCcopy number gain, and deletion events associated withSPOPmutation. Overall, African-derived tumours were 2-fold more likely to present with a hyper-SV subtype. In addition to hyper-duplication and deletion subtypes, we describe a new hyper-translocation subtype. While we confirm a lowerTMPRSS2-ERGfusion-positive rate in tumours from African cases (10%versus33%), novel African-specific PCa ETS family member andTMPRSS2fusion partners were identified, includingLINC01525, FBXO7,GTF3C2,NTNG1andYPEL5. Notably, we found 74 somatic SV hotspots impacting 18 new candidate driver genes, withCADM2,LSAMP,PTPRD,PDE4DandPACRGhaving therapeutic implications for African patients.ConclusionsIn this first African-inclusive SV study for high-risk PCa, we demonstrate the power of SV interrogation for the identification of novel subtypes, oncogenic drivers and therapeutic targets. Identifying a novel spectrum of SVs in tumours derived from African patients provides a mechanism that may contribute, at least in part, to the observed ethnic disparity in advanced PCa presentation in men of African ancestry.
Clinical trial design in the era of precision medicine
Authors: Fountzilas Elena , Tsimberidou Apostolia M. , Vo Henry Hiep , Kurzrock Razelle 
Published: August 2022

AbstractRecent rapid biotechnological breakthroughs have led to the identification of complex and unique molecular features that drive malignancies. Precision medicine has exploited next-generation sequencing and matched targeted therapy/immunotherapy deployment to successfully transform the outlook for several fatal cancers. Tumor and liquid biopsy genomic profiling and transcriptomic, immunomic, and proteomic interrogation can now all be leveraged to optimize therapy. Multiple new trial designs, including basket and umbrella trials, master platform trials, and N-of-1 patient-centric studies, are beginning to supplant standard phase I, II, and III protocols, allowing for accelerated drug evaluation and approval and molecular-based individualized treatment. Furthermore, real-world data, as well as exploitation of digital apps and structured observational registries, and the utilization of machine learning and/or artificial intelligence, may further accelerate knowledge acquisition. Overall, clinical trials have evolved, shifting from tumor type-centered to gene-directed and histology-agnostic trials, with innovative adaptive designs and personalized combination treatment strategies tailored to individual biomarker profiles. Some, but not all, novel trials now demonstrate that matched therapy correlates with superior outcomes compared to non-matched therapy across tumor types and in specific cancers. To further improve the precision medicine paradigm, the strategy of matching drugs to patients based on molecular features should be implemented earlier in the disease course, and cancers should have comprehensive multi-omic (genomics, transcriptomics, proteomics, immunomic) tumor profiling. To overcome cancer complexity, moving from drug-centric to patient-centric individualized combination therapy is critical. This review focuses on the design, advantages, limitations, and challenges of a spectrum of clinical trial designs in the era of precision oncology.
Mucin O-glycan-microbiota axis orchestrates gut homeostasis in a diarrheal pig model
Authors: Xia Bing , Zhong Ruqing , Wu Weida , Luo Chengzeng , Meng Qingshi , Gao Qingtao , Zhao Yong , Chen Liang , Zhang Sheng , Zhao Xin , Zhang Hongfu 
Published: August 2022

Abstract
Background
Post-weaning diarrhea in piglets reduces growth performance and increases mortality, thereby causing serious economic losses. The intestinal epithelial cells and microbiota reciprocally regulate each other in order to maintain intestinal homeostasis and control inflammation. However, a relative paucity of research has been focused on the host-derived regulatory network that controls mucin O-glycans and thereby changes gut microbiota during diarrhea in infancy. At the development stage just after birth, the ontogeny of intestinal epithelium, immune system, and gut microbiota appear similar in piglets and human infants. Here, we investigated the changes of mucin O-glycans associated with gut microbiota using a diarrheal post-weaned piglet model.

Results
We found that diarrhea disrupted the colonic mucus layer and caused aberrant mucin O-glycans, including reduced acidic glycans and truncated glycans, leading to an impaired gut microenvironment. Subsequently, the onset of diarrhea, changes in microbiota and bacterial translocation, resulting in compromised epithelial barrier integrity, enhanced susceptibility to inflammation, and mild growth faltering. Furthermore, we found the activation of NLRP3 inflammasome complexes in the diarrheal piglets when compared to the healthy counterparts, triggered the release of proinflammatory cytokines IL-1β and IL-18, and diminished autophagosome formation, specifically the defective conversion of LC3A/B I into LC3A/B II and the accumulation of p62. Additionally, selective blocking of the autophagy pathway by 3-MA led to the reduction in goblet cell-specific gene transcript levels in vitro.

Conclusions
We observed that diarrheal piglets exhibited colonic microbiota dysbiosis and mucosal barrier dysfunction. Our data demonstrated that diarrhea resulted in the activation of inflammasomes and autophagy restriction along with aberrant mucin O-glycans including reduced acidic glycans and truncated glycans. The results suggested the mucin O-glycans-microbiota axis is likely associated with diarrheal pathogenesis. Our study provides novel insights into the pathophysiology of early-weaning-induced diarrheal disease in piglets and potentially understanding of disease mechanisms of diarrhea for human infants. Understanding the molecular pathology and pathogenesis of diarrhea is a prerequisite for the development of novel and effective therapies. Our data suggest that facilitating O-glycan elongation, modifying the microbiota, and developing specific inhibitors to some key inflammasomes could be the options for therapy of diarrhea including human infants.

Graphical abstract
α-Dystrobrevin knockout mice have increased motivation for appetitive reward and altered brain cannabinoid receptor 1 expression
Authors: Hawkes Cheryl A. , Heath Christopher J. , Sharp Matthew M. , Górecki Dariusz C. , Carare Roxana O. 
Published: August 2022

Abstractα-Dystrobrevin (α-DB) is a major component of the dystrophin-associated protein complex (DAPC). Knockout (KO) of α-DB in the brain is associated with astrocytic abnormalities and loss of neuronal GABA receptor clustering. Mutations in DAPC proteins are associated with altered dopamine signaling and cognitive and psychiatric disorders, including schizophrenia. This study tested the hypothesis that motivation and associated underlying biological pathways are altered in the absence of α-DB expression. Male wildtype and α-DB KO mice were tested for measures of motivation, executive function and extinction in the rodent touchscreen apparatus. Subsequently, brain tissues were evaluated for mRNA and/or protein levels of dysbindin-1, dopamine transporter and receptor 1 and 2, mu opioid receptor 1 (mOR1) and cannabinoid receptor 1 (CB1). α-DB KO mice had significantly increased motivation for the appetitive reward, while measures of executive function and extinction were unaffected. No differences were observed between wildtype and KO animals on mRNA levels of dysbindin-1 or any of the dopamine markers. mRNA levels of mOR1were significantly decreased in the caudate-putamen and nucleus accumbens of α-DB KO compared to WT animals, but protein levels were unaltered. However, CB1 protein levels were significantly increased in the prefrontal cortex and decreased in the nucleus accumbens of α-DB KO mice. Triple-labelling immunohistochemistry confirmed that changes in CB1 were not specific to astrocytes. These results highlight a novel role for α-DB in the regulation of appetitive motivation that may have implications for other behaviours that involve the dopaminergic and endocannabinoid systems.
Isolated MLH1 Loss by Immunohistochemistry Because of Benign Germline MLH1 Polymorphisms
Authors: Bosch Dustin E. , Yeh Matthew M. , Salipante Stephen J. , Jacobson Angela , Cohen Stacey A. , Konnick Eric Q. , Paulson Vera A. 
Published: August 2022

PURPOSE Mismatch repair (MMR) immunohistochemistry (IHC) is frequently used to inform prognosis, select (immuno-)therapy, and identify patients for heritable cancer syndrome testing. However, false-negative and false-positive MMR IHC interpretations have been described. MATERIALS AND METHODS Following identification of discordant MMR IHC and DNA-based microsatellite instability testing in a patient with colorectal carcinoma, we retrospectively reviewed institutional archives to identify patient samples with similar discrepancies. RESULTS We report a patient with metastatic colorectal carcinoma who initially received immunotherapy on the basis of apparent isolated loss of MLH1 by IHC; notably, MLH1 promoter hypermethylation was negative. Subsequent evaluation of neoplastic tissue on a DNA-based targeted next-generation sequencing panel demonstrated microsatellite stability, low tumor mutational burden, and a benign MLH1 variant, MLH1 p.V384D, accompanied by loss of heterozygosity. The constellation of findings and repeat MLH1 IHC demonstrating retained expression using a different antibody-clone, supported reclassification of the neoplasm as MMR-proficient. Immunotherapy was discontinued, and cytotoxic chemotherapy was initiated. This index case of apparent discordance between MMR IHC and DNA-based microsatellite instability prompted a retrospective review of institutional archives to identify patient samples with similar discrepancies. Further evaluation of neoplasms harboring MLH1 p.V384D with loss of heterozygosity revealed systematic antibody-dependent interference. The review also identified a second IHC-interference candidate, MLH1 p.A441T. CONCLUSION This study confirms that rare germline polymorphisms can result in incorrect IHC results, potentially affecting selection of optimal therapy and the decision to pursue germline testing. This case further highlights the need for expert molecular pathologic review and communication between clinical and molecular oncology teams.
Immune Checkpoint Blockade Outcome in Small-Cell Lung Cancer and Its Relationship With Retinoblastoma Mutation Status and Function
Authors: Dowlati Afshin , Abbas Ata , Chan Timothy , Henick Brian , Wang Xuya , Doshi Parul , Fu Pingfu , Patel Jyoti , Kuo Fengshen , Chang Han , Balli David 
Published: August 2022

PURPOSEImmune checkpoint blockade (ICB) in conjunction with chemotherapy is approved for the treatment of extensive-stage small-cell lung cancer (SCLC). Although specific genomic abnormalities such as KEAP1 and STK11 gene mutations are associated with resistance to ICB in non-SCLC, no genomic abnormality has been found in association with resistance to ICB in SCLC.MATERIALS AND METHODSWe first analyzed a retrospective cohort of 42 patients with SCLC treated with single-agent ICB or ICB combination (data set A). We then validated our results in a large prospective clinical trial of 460 patients (CheckMate 032, data set B). DNA and RNA sequencing were performed.RESULTSIn data set A, patients treated with ICB with RB1 wild-type (WT) had a median overall survival (OS) of 23.1 months (95% CI, 9 to 37.5), whereas the RB1 mutant OS was 5 months (95% CI, 2.5 to 26; P = .04). Differentially expressed gene analysis between RB1 mutant and RB1 WT samples indicated the enrichment of downregulated immune-related genes and an immune exclusion phenotype among RB1 mutant but not in the RB1 WT tumor samples. We then assessed results from 460 patients enrolled in CheckMate 032, a trial of nivolumab (NIVO) or NIVO + ipilimumab only in SCLC. In this large cohort, RB1 WT patients had significantly improved outcome with NIVO therapy compared with mutant patients (hazard ratio, 1.41; 95% CI, 1.02 to 2.01; P = .041). High RB1 loss-of-function (LOF) signature scores significantly associated with neuroendocrine subtypes (ASCL1 and NeuroD1). However, neuroendocrine subtypes did not associate with OS. Remarkably, patients with lower RB1 LOF scores had longer OS following treatment with NIVO.CONCLUSIONSCLC patients with RB1 WT status or lower RB1 LOF signature scores by transcriptomics have better outcomes with ICB monotherapy.
Clinical efficacy of motor imagery therapy based on fNIRs technology in rehabilitation of upper limb function after acute cerebral infarction
Authors: Dai Yi , Huang Fang , Zhu Yanfang 
Published: August 2022

Objective: To investigate the efficacy of motor imagery therapy (MIT) based on functional near-infrared spectroscopy (fNIRs) technology in rehabilitation of upper limb function after cerebral infarction, so as to provide guidance for clinical practice.
Methods: A total of 84 patients with upper limb dysfunction after acute cerebral infarction admitted to Wuhan Puren Hospital from January 2020 to January 2021 were included in this study and randomly divided into two groups based on random number table method: experimental group and control group, with 42 cases in each group. Both groups were given active symptomatic treatment. The control group received conventional exercise rehabilitation, while the experimental group also received MIT based on fNIRs technology in addition to the treatment method adopted by the control group, lasting for eight weeks. The simplified Fugl-Meyer scale was utilized to evaluate the recovery of upper limb function, and the changes of Oxy-Hb and Deoxy-Hb concentrations in the frontal area of brain tissue were measured to evaluate the total effective rate of clinical rehabilitation.
Results: At four and eight weeks of treatment, the Fugl-Meyer scores of the two groups were significantly higher than those before treatment (P<0.05), and those in experimental group were significantly higher than those in control group (P<0.05), with no significant difference before treatment (P>0.05). After treatment, Oxy-Hb concentration in the experimental group was higher than that in the control group (P<0.05), while Deoxy-Hb concentration was lower than that in the control group, with a statistical significance (P<0.05). The total effective rate of rehabilitation in the experimental group was 88.10%, which was significantly higher than 73.81% in the control group (P<0.05).
Conclusion: Motor imagery therapy (MIT) Based on fNIRs technology has important clinical value in rehabilitation of upper limb function after cerebral infarction and is superior to conventional exercise rehabilitation alone, boasting a variety of effects, such as improving the curative effect, ameliorating blood oxygen in brain tissue, and promoting the rehabilitation of upper limb function of patients.
Randomized Controlled Trial: RCT Registration Number is ChiCTR1800015546.
doi: https://doi.org/10.12669/pjms.38.7.5344
How to cite this:Dai Y, Huang F, Zhu Y. Clinical efficacy of motor imagery therapy based on fNIRs technology in rehabilitation of upper limb function after acute cerebral infarction. Pak J Med Sci. 2022;38(7):1980-1985. doi: https://doi.org/10.12669/pjms.38.7.5344
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Informal Legacy and Exporting Among Sub-Saharan African Firms
Authors: Larsen Marcus M. , Witte Caroline T. 
Published: August 2022

Around the world and especially in areas of widespread poverty, firms start their operations without registering with relevant authorities (i.e., in the informal economy). We explore whether firms that initiated their operations in the informal economy but later register have a higher propensity to export than firms that register at the time of their foundation. We reason that the experience of having operated informally provides formally registered firms with the advantage of low-cost and flexible exploration but also a domestic legitimacy liability. We suggest that these factors likely contribute to making foreign export markets more attractive after registration. Based on a comprehensive sample of sub-Saharan African firms, we find that, conditional on registration, firms with an informal legacy have a higher propensity to initiate exporting than firms that started their operations formally. We contribute with theoretical and policy-oriented insights on the dynamics of informality and exporting.Funding: The work of M. M. Larsen was supported by the Carlsbergfondet [Grant CF17_0384].