bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review on the available treatment modalities for Bacillus Calmette–Guérin-unresponsive carcinoma in situ and tumors in patients who are ineligible for or decline radical cystectomy
Authors: Syed Saad , Rahman Mansoor , Israr Aisha , Anwar Masroor , Khatroth Sumalatha , Safi Danish , Kamran Amir 
Published: March 2023

Introduction: Globally, urothelial bladder carcinoma is a disease which carries a poor prognosis. There are various treatment modalities for urothelial bladder carcinoma with intravesical Bacillus Calmette–Guérin immunotherapy being the most efficacious intravesical therapy and the treatment of choice for patients with carcinoma in situ. A number of chemotherapeutic drugs are also available for the management of Ta/T1 tumors such as mitomycin C and epirubicin. However, relapse and progression is quite common. The optimal management of patients with Bacillus Calmette–Guérin-unresponsive disease remains to be a challenge. The purpose of this study was to conduct a systematic review on the treatment modalities available for the management of Bacillus Calmette–Guérin-unresponsive carcinoma in situ and urothelial bladder carcinoma in patients who are ineligible or decline radical cystectomy. Methods: Two authors independently searched three databases on the treatment modalities available for the management of Bacillus Calmette–Guérin-unresponsive carcinoma in situ and Bacillus Calmette–Guérin-unresponsive urothelial bladder carcinoma. Results: The systematic search resulted in 15 studies. We recommend the use of intravesical CG0070 adenovirus or hyperthermic intravesical chemotherapy mitomycin C in patients with carcinoma in situ only disease. In patients with carcinoma in situ ± Ta/T1 disease, we recommend the use of intravesical radiofrequency-induced chemohyperthermia or electromotive drug administration of mitomycin C. In patients who have Ta/T1 disease, we recommend the use of either hyperthermic intravesical chemotherapy epirubicin or electromotive drug administration mitomycin C followed by chemohyperthermia mitomycin C. If any of these second line therapies fail, an alternative regimen would be a combination of gemcitabine, cabazitaxel, and cisplatin. Conclusion: This recommendation is subject to the available resources and clinical expertise available in different hospitals. More studies using study designs such as randomized controlled trials comparing multiple drugs with larger sample sizes and regular follow-up intervals should be performed to accurately assess the different medications and aid in designing guidelines to guide the management of Bacillus Calmette–Guérin-unresponsive non-muscle invasive intravesical bladder cancer.
Arthroscopically Assisted Anterior Bone Block for Shoulder Instability
Authors: Barnes Ryan H. , Swinehart S. Dane , Rauck Ryan C. , Cvetanovich Gregory L. 
Published: March 2023

Background: Shoulder instability is a common complaint, with treatment depending on the severity of the bony defect. Advancements in arthroscopic techniques have allowed for a less invasive surgery with decreased postoperative pain, improved graft placement, and better visualization. Indications: Large bony defects of the glenoid require bone block augmentation to reduce recurrent instability. In this presentation, arthroscopically assisted anterior bone block was performed with a distal tibial allograft to address recurrent anterior shoulder instability with a large glenoid defect. Technique Description: The patient is placed in a lateral decubitus position. Standard arthroscopic portals are made. The bone block is fashioned from a distal tibial allograft. Using a guide, drill holes are placed in the bone block. The guide is inserted from the posterior portal and placed parallel to the joint surface. Using drill sleeves, superior and inferior screw holes are drilled and a metal cannula is left in place to allow for shuttling of suture. Two anchors are placed on the glenoid to allow for capsule labral junction to be brought up to the graft once the graft is in place. The bone block is delivered through a dilated anterior portal and reduced. The sutures are tensioned. A button is placed on each set of looped sutures, a Nice knot is placed into each, and a tensioning device is tensioned. Once compression is achieved, knots are tied to perform final fixation over the buttons. A suture passing device is used to grab inferior capsule and labrum to the priorly placed anchor on the inferior glenoid and tied. Results: Arthroscopically assisted anterior bone block for shoulder instability has been demonstrated to have similar clinical and radiographic outcomes when compared with open treatment. However, arthroscopically assisted Latarjet has been shown to have decreased soft tissue disruption and possible improvements in graft placement. Discussion/Conclusion: Arthroscopically assisted anterior bone block is a technically demanding surgery but has been shown to have similar outcomes when compared with open treatment. In this video, we demonstrate an arthroscopically assisted anterior bone block for recurrent anterior shoulder instability. Patient Consent Disclosure Statement: The author(s) attests that consent has been obtained from any patient(s) appearing in this publication. If the individual may be identifiable, the author(s) has included a statement of release or other written form of approval from the patient(s) with this submission for publication.
Monocyte migration profiles define disease severity in acute COVID-19 and unique features of long COVID
Authors: Scott Nicholas A. , Pearmain Laurence , Knight Sean B. , Brand Oliver , Morgan David J. , Jagger Christopher , Harbach Sarah , Khan Saba , Shuwa Halima A. , Franklin Miriam , Kästele Verena , Williams Thomas , Prise Ian , McClure Flora A. , Hackney Pamela , Smith Lara , Menon Madhvi , Konkel Joanne E. , Lawless Criag , Wilson James , Mathioudakis Alexander G. , Stanel Stefan C. , Ustianowski Andrew , Lindergard Gabriella , Brij Seema , Diar Bakerly Nawar , Dark Paul , Brightling Christopher , Rivera-Ortega Pilar , Lord Graham M. , Horsley Alex ,   CIRCO, Piper Hanley Karen , Felton Timothy , Simpson Angela , Grainger John R. , Hussell Tracy , Mann Elizabeth R. 
Published: March 2023

BackgroundCOVID-19 is associated with a dysregulated immune response but it is unclear how immune dysfunction contributes to the chronic morbidity persisting in many COVID-19 patients during convalescence (long COVID).MethodsWe assessed phenotypical and functional changes of monocytes in COVID-19 patients during hospitalisation and up to 9 months of convalescence following COVID-19, respiratory syncytial virus or influenza A. Patients with progressive fibrosing interstitial lung disease were included as a positive control for severe, ongoing lung injury.ResultsMonocyte alterations in acute COVID-19 patients included aberrant expression of leukocyte migration molecules, continuing into convalescence (n=142) and corresponding with specific symptoms of long COVID. Long COVID patients with unresolved lung injury, indicated by sustained shortness of breath and abnormal chest radiology, were defined by high monocyte expression of C-X-C motif chemokine receptor 6 (CXCR6) (p<0.0001) and adhesion molecule P-selectin glycoprotein ligand 1 (p<0.01), alongside preferential migration of monocytes towards the CXCR6 ligand C-X-C motif chemokine ligand 16 (CXCL16) (p<0.05), which is abundantly expressed in the lung. Monocyte CXCR6 and lung CXCL16 were heightened in patients with progressive fibrosing interstitial lung disease (p<0.001), confirming a role for the CXCR6–CXCL16 axis in ongoing lung injury. Conversely, monocytes from long COVID patients with ongoing fatigue exhibited a sustained reduction of the prostaglandin-generating enzyme cyclooxygenase 2 (p<0.01) and CXCR2 expression (p<0.05). These monocyte changes were not present in respiratory syncytial virus or influenza A convalescence.ConclusionsOur data define unique monocyte signatures that define subgroups of long COVID patients, indicating a key role for monocyte migration in COVID-19 pathophysiology. Targeting these pathways may provide novel therapeutic opportunities in COVID-19 patients with persistent morbidity.
Exercise intolerance in post-coronavirus disease 2019 survivors after hospitalisation
Authors: Lafetá Mariana L. , Souza Vitor C. , Menezes Thaís C.F. , Verrastro Carlos G.Y. , Mancuso Frederico J. , Albuquerque André Luis P. , Tanni Suzana E. , Izbicki Meyer , Carlstron Júlio P. , Nery Luiz Eduardo , Oliveira Rudolf K.F. , Sperandio Priscila A. , Ferreira Eloara V.M. 
Published: March 2023

RationalePost-coronavirus disease 2019 (COVID-19) survivors frequently have dyspnoea that can lead to exercise intolerance and lower quality of life. Despite recent advances, the pathophysiological mechanisms of exercise intolerance in the post-COVID-19 patients remain incompletely characterised. The objectives of the present study were to clarify the mechanisms of exercise intolerance in post-COVID-19 survivors after hospitalisation.MethodsThis prospective study evaluated consecutive patients previously hospitalised due to moderate-to-severe/critical COVID-19. Within mean±sd90±10 days of onset of acute COVID-19 symptoms, patients underwent a comprehensive cardiopulmonary assessment, including cardiopulmonary exercise testing with earlobe arterialised capillary blood gas analysis.Measurements and main results87 patients were evaluated; mean±sdpeak oxygen consumption was 19.5±5.0 mL·kg−1·min−1, and the tertiles were ≤17.0, 17.1–22.2 and ≥22.3 mL·kg−1·min−1. Hospitalisation severity was similar among the three groups; however, at the follow-up visit, patients with peak oxygen consumption ≤17.0 mL·kg−1·min−1reported a greater sensation of dyspnoea, along with indices of impaired pulmonary function, and abnormal ventilatory, gas-exchange and metabolic responses during exercise compared to patients with peak oxygen consumption >17 mL·kg−1·min−1. By multivariate logistic regression analysis (receiver operating characteristic curve analysis) adjusted for age, sex and prior pulmonary embolism, a peak dead space fraction of tidal volume ≥29 and a resting forced vital capacity ≤80% predicted were independent predictors of reduced peak oxygen consumption.ConclusionsExercise intolerance in the post-COVID-19 survivors was related to a high dead space fraction of tidal volume at peak exercise and a decreased resting forced vital capacity, suggesting that both pulmonary microcirculation injury and ventilatory impairment could influence aerobic capacity in this patient population.
Single-cell transcriptome reveals Staphylococcus aureus modulating fibroblast differentiation in the bone-implant interface
Authors: Yu Jinlong , Wang Boyong , Zhang Feiyang , Ren Zun , Jiang Feng , Hamushan Musha , Li Mingzhang , Guo Geyong , Shen Hao 
Published: March 2023

Abstract
Background
This study aimed to delineate the cell heterogeneity in the bone-implant interface and investigate the fibroblast responses to implant-associated S. aureus infection.

Methods
Single-cell RNA sequencing of human periprosthetic tissues from patients with periprosthetic joint infection (PJI, n = 3) and patients with aseptic loosening (AL, n = 2) was performed. Cell type identities and gene expression profiles were analyzed to depict the single-cell landscape in the periprosthetic environment. In addition, 11 publicly available human scRNA-seq datasets were downloaded from GSE datasets and integrated with the in-house sequencing data to identify disease-specific fibroblast subtypes. Furthermore, fibroblast pseudotime trajectory analysis and Single-cell regulatory network inference and clustering (SCENIC) analysis were combined to identify transcription regulators responsible for fibroblast differentiation. Immunofluorescence was performed on the sequenced samples to validate the protein expression of the differentially expressed transcription regulators.

Results
Eight major cell types were identified in the human bone-implant interface by analyzing 36,466 cells. Meta-analysis of fibroblasts scRNA-seq data found fibroblasts in the bone-implant interface express a high level of CTHRC1. We also found fibroblasts could differentiate into pro-inflammatory and matrix-producing phenotypes, each primarily presented in the PJI and AL groups, respectively. Furthermore, NPAS2 and TFEC which are activated in PJI samples were suggested to induce pro-inflammatory polarization in fibroblasts, whereas HMX1, SOX5, SOX9, ZIC1, ETS2, and FOXO1 are matrix-producing regulators. Meanwhile, we conducted a CMap analysis and identified forskolin as a potential regulator for fibroblast differentiation toward matrix-producing phenotypes.

Conclusions
In this study, we discovered the existence of CTHRC1+ fibroblast in the bone-implant interface. Moreover, we revealed a bipolar mode of fibroblast differentiation and put forward the hypothesis that infection could modulate fibroblast toward a pro-inflammatory phenotype through NPAS2 and TFEC.
Unravelling the limb regeneration mechanisms of Polypedates maculatus, a sub-tropical frog, by transcriptomics
Authors: Mahapatra Cuckoo , Naik Pranati , Swain Sumanta Kumar , Mohapatra Pratyush Paradarsita 
Published: March 2023

Abstract
Background
Regeneration studies help to understand the strategies that replace a lost or damaged organ and provide insights into approaches followed in regenerative medicine and engineering. Amphibians regenerate their limbs effortlessly and are indispensable models to study limb regeneration. Xenopus and axolotl are the key models for studying limb regeneration but recent studies on non-model amphibians have revealed species specific differences in regeneration mechanisms.

Results
The present study describes the de novo transcriptome of intact limbs and three-day post-amputation blastemas of tadpoles and froglets of the Asian tree frog Polypedates maculatus, a non-model amphibian species commonly found in India. Differential gene expression analysis between early tadpole and froglet limb blastemas discovered species-specific novel regulators of limb regeneration. The present study reports upregulation of proteoglycans, such as epiphycan, chondroadherin, hyaluronan and proteoglycan link protein 1, collagens 2,5,6, 9 and 11, several tumour suppressors and methyltransferases in the P. maculatus tadpole blastemas. Differential gene expression analysis between tadpole and froglet limbs revealed that in addition to the expression of larval-specific haemoglobin and glycoproteins, an upregulation of cysteine and serine protease inhibitors and downregulation of serine proteases, antioxidants, collagenases and inflammatory genes in the tadpole limbs were essential for creating an environment that would support regeneration. Dermal myeloid cells were GAG+, EPYC+, INMT+, LEF1+ and SALL4+ and seemed to migrate from the unamputated regions of the tadpole limb to the blastema. On the other hand, the myeloid cells of the froglet limb blastemas were few and probably contributed to sustained inflammation resulting in healing.

Conclusions
Studies on non-model amphibians give insights into alternate tactics for limb regeneration which can help devise a plethora of methods in regenerative medicine and engineering.
Neuroprotective effects of vinpocetine, as a phosphodiesterase 1 inhibitor, on long-term potentiation in a rat model of Alzheimer’s disease
Authors: Shekarian Meysam , Salehi Iraj , Raoufi Safoura , Asadbegi Masoumeh , Kourosh-Arami Masoumeh , Komaki Alireza 
Published: March 2023

Abstract
Background
Vinpocetine (Vin) is known as a phosphodiesterase 1 inhibitor (PDE1-I) drug with multilateral effects, including antioxidant and anti-inflammatory activity. In this research, we investigated the neuroprotective and therapeutic effects of Vin through hippocampal synaptic plasticity on a rat’s model of Alzheimer’s disease (AD) induced by an intracerebroventricular (ICV) injection of beta-amyloid (Aβ).

Methods
Sixty adult male Wistar rats were randomly divided into six groups: 1. control, 2. sham, 3. Aβ, 4. pretreatment (Vin + Aβ): Vin (4 mg/kg, gavage) for 30 days and then, inducing an AD model by an ICV injection of Aβ(1–42), 5. treatment (Aβ + Vin): inducing an AD model and then receiving Vin for 30 days by gavage, and 7. pretreatment + treatment (Vin + Aβ + Vin): receiving Vin by gavage for 30 days before and 30 days after the induction of an AD model. After these procedures, via stereotaxic surgery, the stimulating electrodes were placed at the perforant pathway (PP) and the recording electrodes were implanted in the dentate gyrus.

Results
Excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitude in the Aβ group meaningfully diminished compared to the control group after the induction of long-term potentiation (LTP).

Conclusions
Vin could significantly prevent the Aβ effects on LTP. It can be concluded that pretreatment and treatment with Vin can be neuroprotective against harmful consequences of Aβ on hippocampal synaptic plasticity.
Factors influencing the timeliness of care for patients with lung cancer in Bangladesh
Authors: Ansar Adnan , Lewis Virginia , McDonald Christine Faye , Liu Chaojie , Rahman Muhammad Aziz 
Published: March 2023

Abstract
Background
This study explored the factors associated with timeliness of care in the healthcare seeking pathway among patients with lung cancer in Bangladesh.

Methods
A structured questionnaire was used for data collection from 418 patients with lung cancer through face-to-face interviews in three tertiary care hospitals. Log-rank tests were performed to test differences in the length of intervals between points in healthcare by socioeconomic characteristics and care seeking behaviours of the patients. Cox Proportional Hazard (PH) regression analysis was performed to identify the predictors of the intervals after adjustment for variations in other variables.

Results
A higher education level was associated significantly (p < 0.05) with a shorter interval between first contact with a healthcare provider (HCP) and diagnosis (median 81 days) and initiation of treatment (median 101 days). Higher monthly household income was associated significantly with a shorter time from first contact and diagnosis (median 91 days), onset of symptom and diagnosis (median 99 days), onset of symptom and treatment (median 122 days), and first contact with any HCP to treatment (median 111 days). Consulting with additional HCPs prior to diagnosis was associated significantly with longer intervals from first contact with any HCP and diagnosis (median 127 days), onset of symptom and diagnosis (median 154 days), onset of symptom and treatment (median 205 days), and first contact with any HCP to treatment (median 174 days). Consulting with informal HCPs was associated significantly with a longer time interval from symptom to treatment (median 171 days). Having more than one triggering symptom was associated significantly with a shorter interval between onset of symptoms and first contact with any HCP.

Conclusion
The predictors for timeliness of lung cancer care used in this study affected different intervals in the care seeking pathway. Higher education and income predicted shorter intervals whereas consulting informal healthcare providers and multiple providers were associated with longer intervals.
Predicting health services utilization using a score of perceived barriers to medical care: evidence from rural Senegal
Authors: Coste Marion , Bousmah Marwân-al-Qays 
Published: March 2023

Abstract
Background
Ensuring access to healthcare services is a key element to achieving the Sustainable Development Goal 3 of “promoting healthy lives and well-being for all” through Universal Health Coverage (UHC). However, in the context of low- and middle-income countries, most studies focused on financial protection measured through catastrophic health expenditures (CHE), or on health services utilization among specific populations exhibiting health needs (such as pregnancy or recent sickness).

Methods
This study aims at building an individual score of perceived barriers to medical care (PBMC) in order to predict primary care utilization (or non-utilization). We estimate the score on six items: (1) knowing where to go, (2) getting permission, (3) having money, (4) distance to the facility, (5) finding transport, and (6) not wanting to go alone, using individual data from 1787 adult participants living in rural Senegal. We build the score via a stepwise descendent explanatory factor analysis (EFA), and assess its internal consistency. Finally, we assess the construct validity of the factor-based score by testing its association (univariate regressions) with a wide range of variables on determinants of healthcare-seeking, and evaluate its predictive validity for primary care utilization.

Results
EFA yields a one-dimensional score combining four items with a 0.7 Cronbach’s alpha indicating good internal consistency. The score is strongly associated—p-values significant at the 5% level—with determinants of healthcare-seeking (including, but not limited to, sex, education, marital status, poverty, and distance to the health facility). Additionally, the score can predict non-utilization of primary care at the household level, utilization and non-utilization of primary care following an individual’s episode of illness, and utilization of primary care during pregnancy and birth. These results are robust to the use of a different dataset.

Conclusion
As a valid, sensitive, and easily documented individual-level indicator, the PBMC score can be a complement to regional or national level health services coverage to measure health services access and predict utilization. At the individual or household level, the PBMC score can also be combined with conventional metrics of financial risk protection such as CHE to comprehensively document deficits in, and progress towards UHC.
Synaptic modifications transform neural networks to function without oxygen
Authors: Amaral-Silva Lara , Santin Joseph M. 
Published: March 2023

Abstract
Background
Neural circuit function is highly sensitive to energetic limitations. Much like mammals, brain activity in American bullfrogs quickly fails in hypoxia. However, after emergence from overwintering, circuits transform to function for approximately 30-fold longer without oxygen using only anaerobic glycolysis for fuel, a unique trait among vertebrates considering the high cost of network activity. Here, we assessed neuronal functions that normally limit network output and identified components that undergo energetic plasticity to increase robustness in hypoxia.

Results
In control animals, oxygen deprivation depressed excitatory synaptic drive within native circuits, which decreased postsynaptic firing to cause network failure within minutes. Assessments of evoked and spontaneous synaptic transmission showed that hypoxia impairs synaptic communication at pre- and postsynaptic loci. However, control neurons maintained membrane potentials and a capacity for firing during hypoxia, indicating that those processes do not limit network activity. After overwintering, synaptic transmission persisted in hypoxia to sustain motor function for at least 2 h.

Conclusions
Alterations that allow anaerobic metabolism to fuel synapses are critical for transforming a circuit to function without oxygen. Data from many vertebrate species indicate that anaerobic glycolysis cannot fuel active synapses due to the low ATP yield of this pathway. Thus, our results point to a unique strategy whereby synapses switch from oxidative to exclusively anaerobic glycolytic metabolism to preserve circuit function during prolonged energy limitations.