bluuebunny/crossref_metadata_2025 huggingface dataset:
Hand Therapy Regimen for Functional Recovery Following Combined Face and Bilateral Hand Transplantation
Authors: Boczar Daniel , Seu Monica , O’Connell April , Gersh Eugene , Chaya Bachar F. , Berman Zoe , Ruiz Natalia , Welsh Laura , Rodriguez Eduardo D.
Published: October 2022

Intensive postoperative rehabilitation therapy is associated with positive functional recovery in hand transplants (HTs). Our goal is to share the hand therapy protocol developed for our patient who underwent a combined face and bilateral HT. The patient is a 23-year-old right-hand-dominant male with a history of third-degree burns to 80% of his body following a motor vehicle accident. A multidisciplinary evaluation established his candidacy for a combined face and bilateral HT, and surgery took place in August 2020. Our individualized hand therapy protocol consisted of 4 phases. The pre-surgery phase focused on planning the orthotics and patient/caregivers’ education on the rehabilitation process. The intensive care unit (ICU)/acute care phase involved hand allograft protection and positioning via orthotic fabrication, safe limb handling, and edema/wound management. The inpatient rehabilitation phase aimed to prepare the patient for independent living via neuromuscular and sensory re-education, improvement of upper extremities strength/flexibility, training basic activities of daily living, and providing a home exercise program (HEP). Finally, the outpatient phase aimed to maximize our patient’s range of motion and independency in performing his routine activities and HEP. The patient’s post-transplant functional outcomes showed a significant improvement compared to the pre-operative baseline. We hope this report sheds light on a comprehensive hand therapy program in HT.
Improved Resource Utilization Using WALANT Hand Surgery in Adolescents
Authors: Long Charles Wyatt , Wilson Ayana , Daniels Christy L. , Brown Morgan E. , Carreon Leah , Robinson Luke
Published: October 2022

Background:

Cost, efficiency, patient preference, and safety have driven utilization of wide awake, local anesthesia, no tourniquet (WALANT) in hand surgery. This is not well documented in adolescents. We hypothesize that the use of WALANT with adolescents reduced time spent in the operating room (OR) and in the hospital when compared with patients who underwent surgery with traditional anesthesia (TA).

Methods:

After institutional review board approval, we performed a retrospective review of patients aged 10 to 17 who underwent surgery at a regional hospital system including the level 1 pediatric trauma hospital. Operative notes were assessed for use of WALANT. We excluded those operations not traditionally amenable to WALANT. Using a propensity matched cohort, hospital time, OR time, and perioperative complications were recorded and compared to evaluate efficiency and perioperative safety.

Results:

There were 28 cases in the WALANT group and 28 cases in the TA group after excluding cases not amenable to WALANT, and cases were propensity matched. Although the operative time (incision to closure) was similar, for WALANT patients, the in-room to procedure time (15 vs 22 minutes), procedure end to out-room time (5 vs 10 minutes), total room time (52.81 vs 63.68), and length of hospital stay (222 vs 342 minutes) were shorter than patients in the TA group.

Conclusion:

Our case series demonstrates time-savings both in the OR and in the hospital overall. Avoiding TA when WALANT is feasible may result in significant savings to hospital systems, patients, and payers while also freeing up anesthesia staff and perioperative nurses.
Discrepancies in Work Relative Value Unit Assignment Based on Operative Time in Hand Surgery
Authors: Cadwell Joshua B. , Weisberger Joseph S. , Gary Cyril S. , Patel Shreya , Maisner Rose S. , Ignatiuk Ashley
Published: October 2022

Background:

Work relative value units (wRVUs) are an intricate component of physician reimbursement determination in the United States. This paper assesses whether wRVUs appropriately consider operative time in hand surgery.

Methods:

The 50 most common single Current Procedural Terminology code hand surgery cases were queried from the 2013 to 2018 National Surgical Quality Improvement Program database. The average assigned wRVUs and median operative times were calculated for each CPT. Linear regressions were calculated between operative time, wRVUs, and wRVUs per hour. Cases deviating the most from the expected wRVUs based on operative time were identified.

Results:

In all, 46 800 cases comprising the top 50 most common hand surgery procedures were identified. Among these cases, the median (range) assigned operative time was 62 minutes (18-110), wRVUs were 7.5 (3.5-18.0), and wRVUs per hour was 8.3 (4.9-14.2). There was a positive linear correlation between operative time and wRVUs ( R2 = 0.60). Each additional operative hour was associated with an additional 6.3 wRVUs ( P < .001). Based on this relationship, the assigned wRVUs for included cases ranged from 59.7% to 172.6% of expected. There was a weak negative relationship between wRVUs per hour and operative time ( R2 = 0.25). Cases shorter than 1 hour had more wRVUs per hour than those longer than 1 hour (10.0 vs. 8.1, P = .003). However, this relationship disappeared when considering case turnover.

Conclusion:

This study suggests a moderately strong positive correlation between wRVUs and operative time in hand surgery. Yet, numerous outliers from this trend exist, suggesting some discrepancies in reimbursement.
Group membership does not modulate goal- versus movement-based imitation
Authors: Genschow Oliver , Pauels Eileen , Krugmann Katrin , Winter Alina
Published: October 2022

It is often put forward that in-group members are imitated more strongly than out-group members. However, the validity of this claim has been questioned as recent investigations were not able to find differences for the imitation of in- versus out-group members. A central characteristic of these failed replications is their mere focus on movement-based imitation, thereby neglecting to take into consideration the superior goal of the movements. By using a computerised version of the pen-and-cups task, we disentangled movement- from goal-based imitation to shed further light onto the link between group membership and imitation. As previous research demonstrated that out-group members (as compared with in-group members) are represented psychologically distant and as psychological distance shifts the degree to which participants engage in goal- versus movement-based imitation, we predicted that in-group members (as compared with out-group members) shift the degree to which individuals imitate movements versus goals. The results did not confirm our predictions, as group membership does not modulate the degree of movement- versus goal-based imitation. Theoretical implications and the question whether imitative behaviour is socially modulated are discussed.
People with intellectual disabilities and borderline intellectual functioning in the Spanish criminal justice system
Authors: L Gómez-Durán Esperanza , Marti-Agustí Gabriel , Martin-Fumadó Carles
Published: October 2022

The way criminal responsibility modifications are applied in intellectual disability and borderline intellectual functioning cases remains empirically unexplored in Spain. We retrieved 100 IQ assessments that involved criminal proceedings, Spanish adult defendants, intelligence quotient testing and intellectual disability/borderline intellectual functioning diagnoses. Intellectual disability and borderline intellectual functioning were diagnosed in 26% and 74% of cases. Intellectual disability diagnoses were significantly associated with forensic doctor support for lack of capacity to be found guilty because of intellectual impairment. Criminal responsibility was modified in 65.8% of convictions and a safety measure was dictated in 10.1%. Courts’ decision of modified responsibility because of intellectual impairment was positively associated with the defendant’s IQ, the forensic diagnosis, the forensic opinion about impaired capacity to be found guilty and the Prosecutor’s position. Any level of intellectual impairment deserves a forensic assessment because of its potential impact on criminal responsibility. Yet, safety measures are underused, so a unique opportunity to help is being missed.
Improving the ‘victim journey’ when reporting domestic abuse cyberstalking to the police – A pilot project evaluation
Authors: Taylor-Dunn Holly , Erol Rosie
Published: October 2022

Criminal justice responses to stalking in England and Wales have come under increased scrutiny following the Joint Criminal Justice Inspectorate report in 2017. In response, police forces throughout England and Wales attempted to improve their handling of stalking. In one UK police force, a project was developed to improve the identification, investigation and victim journey for domestic abuse cyberstalking offences. The project included a specialist investigation team along with a dedicated and co-located Independent Domestic Violence Advisor. This article draws on research conducted during the evaluation of the project and will evidence high levels of victim engagement, positive reports from victims and a 100% success rate in obtaining restraining orders. These findings highlight the valuable role of specialist teams with integrated, independent support for victims and suggest that the victim journey can be improved through collaborative projects between the police and specialist organisations.
Alemtuzumab-induced alopecia universalis and transient accommodation spasm in a patient with multiple sclerosis
Authors: Tzanetakos Dimitrios , Breza Marianthi , Tzartos John S. , Bontzos Georgios , Vakrakou Aigli G. , Dermentzoglou Alexandros , Gkizis Ilias , Smoustopoulos Georgios , Evangelopoulos Maria-Eleptheria , Stefanis Leonidas , Kilidireas Costantinos
Published: October 2022

Herein, we report a case of alopecia universalis and transient accommodation spasm presented after alemtuzumab administration in a patient previously treated with fingolimod. To the best of our knowledge, this is the first report of accommodation spasm as an acute adverse effect of alemtuzumab. Treatment with alemtuzumab in relapsing-remitting multiple sclerosis has been identified as a risk factor for developing secondary autoimmunity within the follow-up period (peak 18–36 months from the first infusion) such as thyroid disorders. This case highlights the need for postmarketing surveillance and the significance of reporting rare side effects related to alemtuzumab; its high efficacy should be weighted with potentially severe adverse events when making a therapeutic decision. Further studies in larger cohorts are needed to elucidate pathomechanisms of alemtuzumab.
Persistence of COVID-19 symptoms beyond 3 months and the delayed return to the usual state of health in Saudi Arabia: A cross-sectional study
Authors: Alkwai Hend M , Khalifa Amany M , Ahmed Ahmed M , Alnajib Alfatih M , Alshammari Khaznah A , Alrashidi Muslima M , Ahmed Hussain G
Published: October 2022

A substantial number of COVID-19 survivors describe ongoing symptoms long after the acute phase. This so-called post-COVID-19 syndrome or long COVID occurs irrespective of initial disease severity.

Objectives:

This cross-sectional study aims to describe and characterise the prevalence of persistent COVID-19 symptoms beyond three months and to evaluate the risk factors for the delayed return to the usual state of health.

Methods:

An electronic survey was developed, piloted, and conducted during the first wave of the COVID-19 pandemic. The survey consisted of questions exploring socio-demographic data, comorbidities, COVID-19 disease (diagnosis, presenting symptoms, management, and persistent symptoms), and the return to the usual state of health. Participants were users of social media platforms. We received results from 746 respondents. One hundred thirty-six responses were excluded due to a self-diagnosis of COVID-19. Respondents reporting a COVID-19 diagnosis 3 months or more prior to the study (N = 213) were included in the analysis. Predictors of the delayed return to the usual state of health were identified by logistic regression.

Results:

Three months or more after a COVID-19 diagnosis, almost half of the respondents, 109 (51.2%), had residual symptoms. The five most prevalent persistent symptoms were fatigue (13.6%), altered sense of smell (12.7%), muscle aches (10.3%), headache (9.9%), and body aches (8.5%). When questioned regarding the return to baseline health, 152 (71.4%) answered in the affirmative. The total number of chronic medical conditions was determined as a statistically significant predictor for the delayed return to the usual state of health.

Conclusion:

Three months or more after acute COVID-19 infection, 5 out of 10 survivors experienced persistent symptoms, and 3 out of 10 reported a delayed return to baseline health. Considering the overall burden of COVID-19 disease, this can pose health and socio-economic challenges. Therefore, health systems need support in managing long COVID and improving long-term COVID-19 outcomes.
Unusual presentation of a common neurosurgical shunt procedure in an adult patient
Authors: Ndongo Sonfack Davaine Joel , Tarabay Bilal , Shedid Daniel , Yuh Sung-Joo
Published: October 2022

Ventriculoperitoneal shunt surgery is one of the treatments of hydrocephalus. It involves placing a shunt from the cerebral ventricles to the peritoneum serving as a drainage point. Infection and catheter blockage are some of the possible complications resulting from this procedure. In some cases, other incidents such as peritoneal shunt migration have also been described. Here, we present the case of a 73-year-old male patient treated with ventriculoperitoneal shunt for a normal pressure hydrocephalus. After an initial blockage of the ventricular catheter, a revision surgery was performed with only mild improvement of his neurological symptoms. A repeat shunt series X-ray showed a migration of the distal catheter into the scrotum through an inguinal hernia. He was successfully treated with a laparoscopic repair of the inguinal hernia and repositioning of the distal catheter into the peritoneal cavity. Scrotal migration and hydrocele are unusual presentations and complications of ventriculoperitoneal shunts. Close follow-up of patients with a ventriculoperitoneal shunt should be performed if they experience worsening of their neurological symptoms. Shunt integrity should be assessed and any complications should be managed.
Pseudo-fever caused by predictive electronic thermometers: A case report
Authors: Maita Hiroki , Kobayashi Tadashi , Akimoto Takashi , Osawa Hiroshi , Kato Hiroyuki
Published: October 2022

A 33-year-old man was referred to our hospital with chief complaints of fever, dizziness, and headache. Although he had recurring fever and dizziness for 7 months, neurological examination, magnetic resonance imaging, computed tomography, electrocardiograms, and blood tests were normal. He was diagnosed with functional hyperthermia, cervical vertigo, and tension headache and was treated with oral medication and physical therapy. After treatment, the dizziness and headache resolved; however, the fever and anxiety did not. During follow-up, he noticed differing results from different electronic thermometers. The physician decided to use an accurate analog thermometer, a gallium thermometer, in combination with the other thermometers. The results differed significantly among the thermometers, and the electronic thermometer readings were found to be inappropriately high. The physician made a diagnosis of pseudo-fever, and the patient recognized that the gallium thermometer’s results were the most accurate reflection of his physical condition, resolving his anxiety.
Myxedema heart disease and non-comatose presentation of myxedema: A case report
Authors: Valenzuela-Vallejo Laura , Folleco-Ortiz Lucila Emilse , Corredor-Orlandelli David , Aguirre-Ruiz Juan Felipe , Isaza Nicolas , Valenzuela-Rincon Alex
Published: October 2022

Myxedema coma is an emergency that develops from non-diagnosed or severe hypothyroidism and requires early recognition and management. Cardiac manifestations are uncommon and pose a challenge in the recognition of myxedema coma. We present the case of a 76-year-old male with a history of thyroidectomy secondary to a follicular carcinoma, who presented with dyspnea, generalized edema, drowsiness, disorientation, memory loss, and episodic generalized tonic-clonic seizures. Antiepileptic and diuretic treatment for seizures and heart failure exacerbation did not improve the symptoms. Further blood analysis revealed a thyroid-stimulating hormone and free thyroxine of 163 mUL/L and 0.64 ng/dL, respectively. Treatment with intravenous hydrocortisone and levothyroxine led to progressive clinical improvement. Uncommon clinical manifestations such as cardiac and non-specific neurologic symptoms should be considered as manifestations of myxedema coma. A comatose mental status is not a universal manifestation, and milder symptoms should be considered. An adequate assessment, including diagnostic scores and prompt hormonal supplementation prevents fatal consequences.
A Case of “Cryptammonia”: Disseminated Cryptococcal Infection Generating Profound Hyperammonemia in a Liver Transplant Recipient
Authors: Phillips Steven M. , Pouch Stephanie M. , Lo Denise J. , Kandiah Sheetal , Lomashvili Koba A. , Subramanian Ram A. , Moran Peter , Killian Alley , Kandiah Prem A.
Published: October 2022

Mycoplasma and Ureaplasma infections have been described as a cause of hyperammonemia syndrome leading to devastating neurological injury in the post-transplant period, most commonly in lung transplant recipients. The occurrence of significant hyperammonemia caused by other urease-producing organisms remains unclear. We describe a case of disseminated cryptococcosis presenting with profound hyperammonemia in a 55-year-old orthotopic liver transplant recipient. Through a process of elimination, other potential causes for hyperammonemia were excluded revealing a probable association between hyperammonemia and disseminated cryptococcosis.
Downregulation of exosomal miR-7-5p promotes breast cancer migration and invasion by targeting RYK and participating in the atypical WNT signalling pathway
Authors: Liang Zhaoyi , Liu Lu , Gao Ruixia , Che Chengchuan , Yang Ge
Published: October 2022

Background

Current studies show that exosomal miRNAs become an important factor in cancer metastasis. Among the many miRNA studies, miR-7-5p has not been thoroughly investigated in breast cancer metastasis.

Methods

Bioinformatic screening was performed using extant data from the GEO database, and miR-7-5p expression levels in breast cancer cell lines and exosomes were further examined using real-time quantitative PCR (qRT-PCR). The extracted exosomes were characterised by transmission electron microscopy (TEM), particle size analysis and marker protein determination. Cell migration and invasion were then examined using wound healing assays and Transwell assays, respectively. Correlation between miR-7-5p and receptor-like tyrosine kinase (RYK) was analysed by luciferase reporter. The effect of miR-7-5p against RYK-related downstream factors was verified using western blot assays.

Results

In this study, we found that the expression of miR-7-5p was significantly different in exosomes secreted from breast cancer cell lines with different high and low invasiveness. Further experiments revealed that miR-7-5p has an important role in inhibiting the migration and invasion of breast cancer. In terms of mechanism of action, miR-7-5p was found to target the RYK, leading to its reduced expression, which in turn caused a reduction in the phosphorylation level of the downstream factor JNK. Reduced levels of phosphorylated JNK factors lead to reduced levels of phosphorylation of c-Jun protein, which in turn leads to increased expression of EMT transcription factors, thereby inhibiting the epithelial–mesenchymal transition (EMT) process to suppress the invasion of breast cancer.

Conclusion

Thus, we demonstrated that exosomes loaded with high levels of miR-7-5p emitted from less aggressive breast cancers can participate in the atypical WNT pathway by targeting the RYK gene and thus inhibit breast cancer metastasis.
Prognostic value of long-term antidiabetic and antihypertensive therapy in postoperative gastric cancer patients: the FIESTA study
Authors: Wang Laicheng , Hu Dan , Fan Zongcheng , Yu Jianjian , Zhang Shunpeng , Lin Yunchai , Chen Xin , Lin Xiandong , Yan Xiyao , Lin Jinxiu , Peng Feng
Published: October 2022

Background

Gastric cancer is often comorbid with hypertension and diabetes mellitus and increases the mortality risk.

Materials and methods

We conducted this prospective cohort study to investigate antidiabetics and antihypertensives’ impact on gastric cancer survival. 3012 patients with gastric carcinoma undergoing radical gastrectomy were enrolled since January 2000 and followed up until July 2020.

Results

Hypertension and diabetes patients had worse survival than patients without hypertension and diabetes [median survival time (MST): 48 versus 112.5 months, p < 0.001 for hypertension, MST: 32.7 versus 183+ months, p < 0.001 for diabetes]. Compared to untreated patients, treated patients had better survival (MST: 109.7 months versus 39.1 months, p < 0.001 for antihypertensives, MST: 120.9 months versus 22.3 months, p < 0.001 for antidiabetics). Antihypertensives and antidiabetics were related to 42% (HR 0.58, 95% CI 0.47–0.73, p < 0.001) and 70% (HR 0.30, 95% CI 0.24–0.38, p < 0.001) reduced mortality risk relative to those without medications. metformin and Calcium channel blockers can better-improved prognosis compared to others (p = 0.00029 and p = 0.015).

Conclusion

Post-surgical gastric cancer patients could benefit substantially from anti-diabetes and antihypertensive therapy. Metformin and Calcium channel blockers may be superior to other medications.
The 4P telehealth business framework for Iran
Authors: Velayati Farnia , Ayatollahi Haleh , Hemmat Morteza , Dehghan Reza
Published: October 2022

Background

Telehealth services can utilize various information technologies and improve quality and efficiency of healthcare delivery by facilitating education, treatment, follow-up, and decision-making. However, these services are not always commercialized, and in case of commercialization, there is no guarantee for their long-term sustainability in market. Therefore, business models and frameworks are used as part of commercialization processes to identify a set of factors affecting the sustainability, effectiveness, and key business activities. The current study aimed to develop a telehealth business framework for Iran.

Methods

This research was conducted in 2021, and a mixed-methods approach was used for data collection. Initially, a telehealth business framework was developed based on the findings derived from a systematic review and a qualitative research. The proposed framework was then reviewed by an expert panel (n = 9) in which the participants had at least three years of work experience in telehealth. Finally, the framework was validated using the Delphi method (three rounds).

Results

The expert panel believed that some components such as partners’ expertise, required capital and financial resources, research and analysis, marketing and branding, tax, product registration, and marketing at scientific congresses and science and technology exhibitions needed to be added to the framework. In the Delphi study, 68 out of 74 components proposed in the initial framework were approved across four major dimensions; namely, prerequisites, production, payments and costs, and post-production services.

Conclusions

It seems that the developed framework can facilitate commercializing telehealth technologies and developing business plans. In addition, telehealth start-ups can use this framework and its various components in a competitive market to be more successful in their businesses. However, it is still critical to evaluate the effectiveness of the framework in practice and in relation to the commercialization of telehealth technologies.
Metabolomics detects clinically silent neuroinflammatory lesions earlier than neurofilament-light chain in a focal multiple sclerosis animal model
Authors: Yeo Tianrong , Bayuangga Halwan , Augusto-Oliveira Marcus , Sealey Megan , Claridge Timothy D. W. , Tanner Rachel , Leppert David , Palace Jacqueline , Kuhle Jens , Probert Fay , Anthony Daniel C.
Published: October 2022

Background

Despite widespread searches, there are currently no validated biofluid markers for the detection of subclinical neuroinflammation in multiple sclerosis (MS). The dynamic nature of human metabolism in response to changes in homeostasis, as measured by metabolomics, may allow early identification of clinically silent neuroinflammation. Using the delayed-type hypersensitivity (DTH) MS rat model, we investigated the serum and cerebrospinal fluid (CSF) metabolomics profiles and neurofilament-light chain (NfL) levels, as a putative marker of neuroaxonal damage, arising from focal, clinically silent neuroinflammatory brain lesions and their discriminatory abilities to distinguish DTH animals from controls.

Methods

1H nuclear magnetic resonance (NMR) spectroscopy metabolomics and NfL measurements were performed on serum and CSF at days 12, 28 and 60 after DTH lesion initiation. Supervised multivariate analyses were used to determine metabolomics differences between DTH animals and controls. Immunohistochemistry was used to assess the extent of neuroinflammation and tissue damage.

Results

Serum and CSF metabolomics perturbations were detectable in DTH animals (vs. controls) at all time points, with the greatest change occurring at the earliest time point (day 12) when the neuroinflammatory response was most intense (mean predictive accuracy [SD]—serum: 80.6 [10.7]%, p < 0.0001; CSF: 69.3 [13.5]%, p < 0.0001). The top discriminatory metabolites at day 12 (serum: allantoin, cytidine; CSF: glutamine, glucose) were all reduced in DTH animals compared to controls, and correlated with histological markers of neuroinflammation, particularly astrogliosis (Pearson coefficient, r—allantoin: r = − 0.562, p = 0.004; glutamine: r = − 0.528, p = 0.008). Serum and CSF NfL levels did not distinguish DTH animals from controls at day 12, rather, significant differences were observed at day 28 (mean [SEM]—serum: 38.5 [4.8] vs. 17.4 [2.6] pg/mL, p = 0.002; CSF: 1312.0 [379.1] vs. 475.8 [74.7] pg/mL, p = 0.027). Neither serum nor CSF NfL levels correlated with markers of neuroinflammation; serum NfL did, however, correlate strongly with axonal loss (r = 0.641, p = 0.001), but CSF NfL did not (p = 0.137).

Conclusions

While NfL levels were elevated later in the pathogenesis of the DTH lesion, serum and CSF metabolomics were able to detect early, clinically silent neuroinflammation and are likely to present sensitive biomarkers for the assessment of subclinical disease activity in patients.
The impacts of implementing recovery innovations: a conceptual framework grounded in qualitative research
Authors: Piat Myra , Wainwright Megan , Rivest Marie-Pier , Sofouli Eleni , von Kirchenheim Tristan , Albert Hélène , Casey Regina , Labonté Lise , O’Rourke Joseph J. , LeBlanc Sébastien
Published: October 2022

Background

Implementing mental health recovery into services is a policy priority in Canada and globally. To that end, a 5 year study was undertaken with seven organisations providing mental health and housing services to people living with a mental health challenge to implement guidelines for the transformation of services and systems towards a recovery-orientation. Multi-stakeholder implementation teams were established and a facilitated process guided teams to choosing and planning for the implementation of one recovery innovation. The recovery innovations chosen were hiring peer support workers, Wellness Recovery Action Planning (WRAP), a family support group, and staff recovery training.

Methods

This study reports on data collected at the post-implementation stage. 90 service users, service providers, family members, managers, other actors and knowledge users participated in 41 group, individual or dyad semi-structured interviews. The interview guides included open-ended questions eliciting participants’ impressions regarding the impact of implementing the innovation on service users, service providers and organisations. We applied a collaborative qualitative content analysis approach in NVivo12 to coding and interpreting the data generated from these questions.

Results

Eighteen impacts of implementing recovery innovations from the perspectives of diverse stakeholder groups were identified. Three impacts of working as an implementation team member and as part of a research project were also identified. Impacts were developed into a conceptual framework organised around four overall categories of impact:Ways of being, Ways of interacting, Ways of thinking, and Ways of operating and doing business.

Conclusions

The IMpacts of Recovery Innovations (IMRI) framework version 1 can assist researchers, evaluators and decision-makers identify, explore and understand impact in the context of recovery innovations. The framework helps fill a gap in conceptualising service and organisation-level impacts. Future research is needed to validate the framework and map it to existing methods for studying impact.
Development and initial validation of a modified lymphocyte transformation test (LTT) assay in patients with DRESS and AGEP
Authors: Weir Chris , Li Jamma , Fulton Richard , Fernando Suran L.
Published: October 2022

Background

The lymphocyte transformation test (LTT) is an in vitro assay used to diagnose drug induced hypersensitivity reactions by detecting the activation and expansion of drug-specific memory T cells to the suspected implicated drug. Traditionally radiolabelled thymidine (3H-thymidine) has been used but requires the handling and disposal of radioactive materials.

Objective

To examine safe alternatives to 3H-thymidine, test assay modifications for improved assay sensitivity and evaluate the modified LTT in patients with DRESS and AGEP.

Methods

Four proliferation detection assays (BRDU, CyQUANT™, MTT and XTT) were screened for LTT sensitivity. XTT the most sensitive and practical was selected for further evaluation Modifications like autologous serum (AS) and regulatory T cell depletion (T-REG) were tested for improved assay sensitivity. Finally, an initial evaluation of the XTT–LTT was performed in 8 patients with DRESS and 2 with AGEP including cytokine testing.

Results

Of the non-radioactive alternatives we tested, XTT a colorimetric assay was the most sensitive and practical to move to evaluation. The addition of AS increased background signal. Depletion of T-REGs improved sensitivity but cell sorting time and risk of contamination limited benefit.

Of eight patients diagnosed with DRESS and 2 with AGEP tested with XTT–LTT assay results showed our assay matched clinical findings of implicated drugs in 8/10 patients when using a stimulation index (SI) ≥ 2 and 8/10 with analysis by ANOVA. All ten patients were correctly diagnosed by either analysis.

Conclusion

XTT appears to be a safe, viable alternative to 3H-thymidine, with high sensitivity and allowing direct cytokine quantification on specific patient cells.
Fat transplantation induces dermal adipose regeneration and reverses skin fibrosis through dedifferentiation and redifferentiation of adipocytes
Authors: Wang Jing , Cai Junrong , Zhang Qian , Wen Jiaqing , Liao Yunjun , Lu Feng
Published: October 2022

Background

Localized scleroderma causes cosmetic disfigurement, joint contractures, and other functional impairment, but no currently available medications can reverse the resulting skin lesions. Fat grafting is beneficial for reversing skin fibrosis; however, the mechanism by which adipose tissue transplantation contributes to lesion improvement has not been fully clarified. The purpose of our study was to verify the therapeutic effect of fat grafts in reversing skin fibrosis.

Methods

Inguinal fat pads from AdipoqCreER+;mT/mG mice, which were treated with tamoxifen, were transplanted to the skin lesion in bleomycin-treated wild-type C57 mice. Tdtomato transgenic mice-derived adipocytes, adipose-derived stem cells (ASCs), dedifferentiated adipocytes (DAs) were embedded in matrigel and transplanted beneath the skin lesion of bleomycin-treated wild-type C57 mice. A transwell co‐culture system was used to verify the effect of ASCs, adipocytes or DAs on scleroderma fibroblasts or monocytes.

Results

Adipocytes from the fat grafts could undergo dedifferentiation and redifferentiation for dermal adipose tissue re-accumulation within the skin lesion. Moreover, compared with ASCs and adipocytes, DAs show greater potency of inducing adipogenesis. ASCs and DAs showed comparable effect on inducing angiogenesis and suppressing macrophage infiltration in fibrotic skin. Co-culture assay showed that DAs and ASCs were able to reduce fibrosis-related genes in human scleroderma fibroblasts and drive M2 macrophage polarization.

Conclusion

Our results indicated that adipocytes would transform into a more functional and dedifferentiated state and reverse dermal fibrosis, by promoting dermal adipose tissue regeneration, improving angiogenesis, suppressing macrophage-mediated inflammation and myofibroblast accumulation.
Evaluation of [68 Ga]Ga-PSMA-I&T PET/CT with additional late scans of the pelvis in prostate-specific antigen recurrence using the PROMISE criteria
Authors: Koehler Daniel , Sauer Markus , Karimzadeh Amir , Apostolova Ivayla , Klutmann Susanne , Adam Gerhard , Knipper Sophie , Maurer Tobias , Berliner Christoph
Published: October 2022

Background

PSMA PET/CT is the recommended imaging test in cases with prostate-specific antigen (PSA) recurrence after primary therapy of prostate cancer (PCa). However, imaging protocols remain a topic of active research. The aim of the presented study was to examine the impact of additional late scans of the pelvis in [68 Ga]Ga-PSMA-I&T PET/CT of patients with rising PSA after prostatectomy.

Methods

A total of 297 patients (median PSA 0.35 ng/ml, interquartile range (IQR) 0.2–0.8) who underwent early whole-body [68 Ga]Ga-PSMA-I&T PET/CT (median dose 141 MBq, IQR 120–163; median 86 min, IQR 56–107) and additional late scans of the pelvis (median 180 min, IQR 170–191) were investigated retrospectively. Early and late images were staged separately according to the PROMISE criteria and compared with a final consensus of both. Standardized uptake values were analyzed for early and late scans.

Results

One hundred and thirty-four (45.1%) [68 Ga]Ga-PSMA-I&T PET/CT showed evidence of recurrent PCa (114/38.4% early, 131/44.1% late). Of 195 lesions, 144 (73.8%) were identified correctly on early scans. 191 (97.9%) lesions were detected on late imaging. The lesion SUVmax (median 3.4, IQR 0.4–6.5 vs. median 3.9, IQR 2.6–8.2) as well as the SUVmax to background ratio (median 9.4, IQR 1.7–19.1 vs. median 15.5, IQR 9.6–34.1) increased significantly between the imaging time points (p < 0.01, respectively). Compared to the final consensus, the miTNM-staging of early scans changed in 58 (19.5%) cases. Of these, 31 patients (10.4%) with negative early scans (T0 N0 M0) were upstaged. Twenty-seven (9.1%) patients with PCa characteristic lesions on early imaging (> T0 N0 M0) were up- and/or downstaged. In 4 (1.3%) cases, PCa-related lesions were only detectable on early PET/CT leading to upstagings of late imaging.

Conclusions

Additional late scans of the pelvis in [68 Ga]Ga-PSMA-I&T PET/CT detected more lesions and an increasing contrast compared to early imaging. This influenced the final miTNM-staging substantially.
Correlation between molar activity, injection mass and uptake of the PARP targeting radiotracer [18F]olaparib in mouse models of glioma
Authors: Chan Chung Ying , Hopkins Samantha L. , Guibbal Florian , Pacelli Anna , Baguña Torres Julia , Mosley Michael , Lau Doreen , Isenegger Patrick , Chen Zijun , Wilson Thomas C. , Dias Gemma , Hueting Rebekka , Gouverneur Véronique , Cornelissen Bart
Published: October 2022

Purpose

Radiopharmaceuticals targeting poly(ADP-ribose) polymerase (PARP) have emerged as promising agents for cancer diagnosis and therapy. PARP enzymes are expressed in both cancerous and normal tissue. Hence, the injected mass, molar activity and potential pharmacological effects are important considerations for the use of radiolabelled PARP inhibitors for diagnostic and radionuclide therapeutic applications. Here, we performed a systematic evaluation by varying the molar activity of [18F]olaparib and the injected mass of [TotalF]olaparib to investigate the effects on tumour and normal tissue uptake in two subcutaneous human glioblastoma xenograft models.

Methods

[18F]Olaparib uptake was evaluated in the human glioblastoma models: in vitro on U251MG and U87MG cell lines, and in vivo on tumour xenograft-bearing mice, after administration of [TotalF]olaparib (varying injected mass: 0.04–8.0 µg, and molar activity: 1–320 GBq/μmol).

Results

Selective uptake of [18F]olaparib was demonstrated in both models. Tumour uptake was found to be dependent on the injected mass of [TotalF]olaparib (µg) but not the molar activity. An injected mass of 1 μg resulted in the highest tumour uptake (up to 6.9 ± 1.3%ID/g), independent of the molar activity. In comparison, both the lower and higher injected masses of [TotalF]olaparib resulted in lower relative tumour uptake (%ID/g; P < 0.05). Ex vivo analysis of U87MG xenograft sections showed that the heterogeneity in [18F]olaparib intratumoural uptake correlated with PARP1 expression. Substantial upregulation of PARP1-3 expression was observed after administration of [TotalF]olaparib (> 0.5 µg).

Conclusion

Our findings show that the injected mass of [TotalF]olaparib has significant effects on tumour uptake. Moderate injected masses of PARP inhibitor-derived radiopharmaceuticals may lead to improved relative tumour uptake and tumour-to-background ratio for cancer diagnosis and radionuclide therapy.
SK3 in POMC neurons plays a sexually dimorphic role in energy and glucose homeostasis
Authors: Yu Meng , Bean Jonathan C. , Liu Hailan , He Yang , Yang Yongjie , Cai Xing , Yu Kaifan , Pei Zhou , Liu Hesong , Tu Longlong , Conde Kristine M. , Wang Mengjie , Li Yongxiang , Yin Na , Zhang Nan , Han Junying , Scarcelli Nikolas A. , Xu Pingwen , He Yanlin , Xu Yong , Wang Chunmei
Published: October 2022

Background

Pro-opiomelanocortin (POMC) neurons play a sexually dimorphic role in body weight and glucose balance. However, the mechanisms for the sex differences in POMC neuron functions are not fully understood.

Results

We detected small conductance calcium-activated potassium (SK) current in POMC neurons. Secondary analysis of published single-cell RNA-Seq data showed that POMC neurons abundantly express SK3, one SK channel subunit. To test whether SK3 in POMC neurons regulates POMC neuron functions on energy and glucose homeostasis, we used a Cre-loxP strategy to delete SK3 specifically from mature POMC neurons. POMC-specific deletion of SK3 did not affect body weight in either male or female mice. Interestingly, male mutant mice showed not only decreased food intake but also decreased physical activity, resulting in unchanged body weight. Further, POMC-specific SK3 deficiency impaired glucose balance specifically in female mice but not in male mice. Finally, no sex differences were detected in the expression of SK3 and SK current in total POMC neurons. However, we found higher SK current but lower SK3 positive neuron population in male POMC neurons co-expressing estrogen receptor α (ERα) compared to that in females.

Conclusion

These results revealed a sexually dimorphic role of SK3 in POMC neurons in both energy and glucose homeostasis independent of body weight control, which was associated with the sex difference of SK current in a subpopulation of POMC + ERα + neurons.
Hyperspectral image denoising and destriping based on sparse representation, graph Laplacian regularization and stripe low-rank property
Authors: Zhang Zhi , Yang Fang
Published: October 2022

During the acquisition of a hyperspectral image (HSI), it is easily corrupted by many kinds of noises, which limits the subsequent applications. For decades, numerous HSI denoising methods have been proposed. However, these methods rarely consider the stripe noise as an independent component, thus cannot effectively remove the stripe noise. In this paper, we propose a mixed noise removal algorithm to destripe an HSI by taking advantage of the low-rank property of stripe noise. In the meantime, sparse representation and graph Laplacian regularization are utilized to remove Gaussian and sparse noise. Roughly speaking, the sparse representation helps achieve the approximation of the original image. A graph Laplacian regularization term can ensure the non-local spatial similarity of an HSI. Separate constraints on the sparse coefficient matrix and stripe noise components can help remove different types of noises. Experimental results on both simulated and real data demonstrate the effectiveness of the proposed method for HSI restoration.
Automated audio captioning: an overview of recent progress and new challenges
Authors: Mei Xinhao , Liu Xubo , Plumbley Mark D. , Wang Wenwu
Published: October 2022

Automated audio captioning is a cross-modal translation task that aims to generate natural language descriptions for given audio clips. This task has received increasing attention with the release of freely available datasets in recent years. The problem has been addressed predominantly with deep learning techniques. Numerous approaches have been proposed, such as investigating different neural network architectures, exploiting auxiliary information such as keywords or sentence information to guide caption generation, and employing different training strategies, which have greatly facilitated the development of this field. In this paper, we present a comprehensive review of the published contributions in automated audio captioning, from a variety of existing approaches to evaluation metrics and datasets. We also discuss open challenges and envisage possible future research directions.
Can serum autoantibodies be a potential early detection biomarker for breast cancer in women? A diagnostic test accuracy review and meta-analysis
Authors: Kathrikolly Thejas , Nair Sreekumaran N. , Mathew Aju , Saxena Prakash P. U. , Nair Suma
Published: October 2022

Background

The increasing incidence of breast cancer necessitates the need to explore alternate screening strategies that circumvent the setbacks of conventional techniques especially among population that report earlier age at diagnosis. Serum autoantibodies is one such potential area of interest. However, their ubiquitous presence across cancer types limits its applicability to any one specific type of cancer. This review was therefore carried out to explore and consolidate available evidence on autoantibodies for early detection of breast cancer and to identify those that demonstrated a higher sensitivity.

Methods

A diagnostic test accuracy (DTA) review was carried out to ascertain serum autoantibodies that could be used for early detection of breast cancer among women. All relevant articles that investigated the role of autoantibodies in early detection of breast cancer were included for the review. MEDLINE, Scopus, ProQuest, Ovid SP, and Cochrane Library were searched extensively for eligible studies. Quality of the included studies was assessed using Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool. RevMan 5.3 was used for exploratory and MetaDTA 2019 for hierarchical analyses. The review helped identify the most frequently investigated autoantibodies and a meta-analysis further consolidated the findings.

Results

A total of 53 articles were included for the final analysis that reported over a 100 autoantibodies that were studied for early detection of breast cancer in women. P53, MUC1, HER2, HSP60, P16, Cyclin B1, and c-Myc were the most frequently investigated autoantibodies. Of these P53, MUC1, HER2, and HSP60 exhibited higher summary sensitivity measures. While the individual pooled sensitivity estimates ranged between 10 and 56%, the panel sensitivity values reported across studies were higher with an estimated range of 60–87%.

Conclusion

Findings from the review indicate a higher sensitivity for an autoantibody panel in comparison to individual assays. A panel comprising of P53, MUC1, HER2, and HSP60 autoantibodies has the potential to be investigated as an early detection biomarker for breast cancer.
Machine learning methods for the study of cybersickness: a systematic review
Authors: Yang Alexander Hui Xiang , Kasabov Nikola , Cakmak Yusuf Ozgur
Published: October 2022

This systematic review offers a world-first critical analysis of machine learning methods and systems, along with future directions for the study of cybersickness induced by virtual reality (VR). VR is becoming increasingly popular and is an important part of current advances in human training, therapies, entertainment, and access to the metaverse. Usage of this technology is limited by cybersickness, a common debilitating condition experienced upon VR immersion. Cybersickness is accompanied by a mix of symptoms including nausea, dizziness, fatigue and oculomotor disturbances. Machine learning can be used to identify cybersickness and is a step towards overcoming these physiological limitations. Practical implementation of this is possible with optimised data collection from wearable devices and appropriate algorithms that incorporate advanced machine learning approaches. The present systematic review focuses on 26 selected studies. These concern machine learning of biometric and neuro-physiological signals obtained from wearable devices for the automatic identification of cybersickness. The methods, data processing and machine learning architecture, as well as suggestions for future exploration on detection and prediction of cybersickness are explored. A wide range of immersion environments, participant activity, features and machine learning architectures were identified. Although models for cybersickness detection have been developed, literature still lacks a model for the prediction of first-instance events. Future research is pointed towards goal-oriented data selection and labelling, as well as the use of brain-inspired spiking neural network models to achieve better accuracy and understanding of complex spatio-temporal brain processes related to cybersickness.
Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options
Authors: Liu Di , Huang Si-Yuan , Sun Jian-Hui , Zhang Hua-Cai , Cai Qing-Li , Gao Chu , Li Li , Cao Ju , Xu Fang , Zhou Yong , Guan Cha-Xiang , Jin Sheng-Wei , Deng Jin , Fang Xiang-Ming , Jiang Jian-Xin , Zeng Ling
Published: October 2022

Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.