bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing essential service provision for prevention and management of violence against women in a remote indigenous community in Amantaní, Peru
Authors: Calderon Maria , Cortez-Vergara Carla , Brown Laura , Lowe Hattie , Abarca Blenda , Rondon Marta , Mannell Jenevieve
Published: October 2023

Background

Women living in indigenous communities in Peru currently experience extremely high rates of intimate partner violence (IPV). Over the past 10 years, there has been a large multi-sectoral initiative to establish a national network of Centros de Emergencia de la Mujer (Women’s Emergency Centres) that integrate health and police services, and substantial increase in efforts from non-governmental organisations in supporting survivors of violence. However, there is currently little evidence on how existing services meet the needs of indigenous women experiencing violence in Peru.

Methods

As part of a broader mixed-methods participatory VAWG prevention study, we assessed existing service provision for women experiencing violence in an indigenous Quechua community from Amantaní, Peru. This involved 17 key informant interviews with legal, government, police, and civil society representatives. We used the UN Women Essential Services Package for Women and Girls Subject to Violence framework to guide our analysis.

Results

Participants identified major gaps in existing services for indigenous women survivors of violence in Peru. They discussed survivors and perpetrators not being identified by the health system, a lack of IPV response training for health professionals, IPV not being prioritised as a health concern, and a lack of health services that are culturally appropriate for indigenous populations. Survivors who report to police are often treated poorly and discriminated against. Legal systems were perceived as insufficient and ineffective, with inadequate legal measures for perpetrators. While legal and policy frameworks exist, they are often not applied in practice. Service provision in this region needs to adopt an intercultural, rights based, gendered approach to IPV response and prevention, considering cultural and linguistic relevance for indigenous populations.

Conclusion

The role of structural violence in perpetuating indigenous women’s experiences of violence and undermining their access to services must be central to designing and implementing appropriate policies and services if they are to meet the needs of indigenous women in Peru.
Autophagy-amplifying nanoparticles evoke immunogenic cell death combined with anti-PD-1/PD-L1 for residual tumors immunotherapy after RFA
Authors: Zhang Shushan , Huang Yongquan , Pi Songying , Chen Hui , Ye Feile , Wu Chaoqun , Li Liujun , Ye Qing , Lin Yuhong , Su Zhongzhen
Published: October 2023

Incomplete radiofrequency ablation (IRFA) triggers mild protective autophagy in residual tumor cells and results in an immunosuppressive microenvironment. This accelerates the recurrence of residual tumors and causes resistance to anti-PD-1/PDL1 therapy, which bringing a great clinical challenge in residual tumors immunotherapy. Mild autophagy activation can promote cancer cell survival while further amplification of autophagy contributes to immunogenic cell death (ICD). To this regard, we constructed active targeting zeolitic imidazolate framework-8 (ZIF-8) nanoparticles (NPs) loaded with STF62247 or both STF62247 and BMS202, namely STF62247@ZIF-8/PEG-FA (SZP) or STF62247-BMS202@ZIF-8/PEG-FA (SBZP) NPs. We found that SZP NPs inhibited proliferation and stimulated apoptosis of residual tumor cells exposed to sublethal heat stress in an autophagy-dependent manner. Further results discovered that SZP NPs could amplify autophagy in residual tumor cells and evoke their ICD, which dramatically boosted the maturation of dendritic cells (DCs). Through vaccination experiments, we found for the first time that vaccination with heat + SZP treatment could efficiently suppress the growth of new tumors and establish long-term immunological memory. Furthermore, SBZP NPs could remarkably promote the ICD of residual tumor cells, obviously activate the anti-tumor immune microenvironment, and significantly inhibit the growth of residual tumors. Thus, amplified autophagy coupled with anti-PD-1/PDL1 therapy is potentially a novel strategy for treating residual tumors after IRFA.

Graphical Abstract
Evaluation of prothrombotic risk of two PROC hotspot mutations (Arg189Trp and Lys193del) in Chinese population: a retrospective study
Authors: Li Lei , Li Jian , Wu Xi , Wu Wenman , Ding Qiulan , Qian Baohua , Wang Xuefeng
Published: October 2023

Background

R189W and K193del of protein C (PC) were hotspot mutations in Chinese population with venous thromboembolism (VTE), but almost two-thirds of patients with above mutations coexisting with other genetically or aquiredly prothrombotic risk factors. The aim of this study is to clarify the independent contributions of R189W or K193del to VTE risk.

Methods

490 unrelated patients with a personal history of VTE and 410 healthy participants were enrolled in this study. Data of their demographics, family history, genetic and acquired thrombosis risk factors were collected and statistically analyzed.

Results

PC R189W and K193del were identified in 3/410 (0.7%) and 7/410 (1.7%) healthy controls, and in 27/490 (5.5%) and 43/490 (8.8%) patients with VTE, respectively. Notably, about 70% of these mutant carriers combined with other genetic or acquired thrombophilic factors. After adjustment for age, gender, other inherited and acquired risk factors, we demonstrated that R189W and K193del were associated with 5.781-fold and 4.365-fold increased risk of VTE, respectively, which were significantly lower than the prothrombotic risk of anticoagulant deficiencies induced from rare mutations. Independent R189W or K193del mutation was not associated with earlier first-onset age as well as higher recurrent rate of VTE. However, combination of other genetic or acquired thrombophilic factors had supra-additive effects on those consequences. The more additional risk factors the patients had, the younger first-onset ages and higher risk of recurrence would be.

Conclusions

As the most frequent mutations for PC deficiency in Chinese population, both R189W and K193del mutations had limited independent contributions to VTE development compared with other rare mutations in PROC gene, but may act in concert with other genetic defects or acquired thrombotic risk factors to produce the final severe phenotype.
Safety and immunogenicity of inactivated Rift Valley Fever Smithburn viral vaccine in sheep
Authors: Matsiela Matome Selina , Naicker Leeann , Khoza Thandeka , Mokoena Nobalanda
Published: October 2023

Background

The live-attenuated Rift Valley Fever Smithburn (SB) vaccine is one of the oldest products widely used in ruminants for control of RVF infections. Vaccinations with RVF Smithburn result in residual pathogenic effect and is limited for use in non-pregnant animals. Commercially available RVFV inactivated vaccines are considered safer options to control the disease. These products are prepared from virulent RVFV isolates and present occupational safety concerns. This research study evaluates the ability of an inactivated SB vaccine strain to elicit neutralising antibody response in sheep.

Methods

The RVF Smithburn vaccine was inactivated with binary ethylenimine at 37 °C. Inactivated RVFV cultures were adjuvanted with Montande™ Gel-01 and aluminium hydroxide (Al (OH)3) gel for immunogenicity and safety determination in sheep. The commercial RVF inactivated vaccine and a placebo were included as positive and negative control groups, respectively.

Results

Inactivated RVFV vaccine formulations were safe with all animals showing no clinical signs of RVFV infection and temperature reactions following prime-boost injections. The aluminium hydroxide formulated vaccine induced an immune response as early as 14 days post primary vaccination with neutralising antibody titre of 1:20 and a peak antibody titre of 1:83 was reached on day 56. A similar trend was observed in the animal group vaccinated with the commercial inactivated RVF vaccine obtaining the highest antibody titre of 1:128 on day 56. The neutralizing antibody levels remained within a threshold for the duration of the study. Merino sheep vaccinated with Montanide™ Gel-01-Smithburn were characterised with overall lower immune response when compared to aluminium hydroxide vaccine emulsions.

Conclusions

These finding suggests that the inactivated RVF Smithburn vaccine strain adjuvanted with aluminium-hydroxide can be used an alternative to the products prepared from virulent RVFV isolates for protection of ruminants against the disease. The vaccine can further be evaluated for safety in pregnant ewes.
The potential use of bacteria and bacterial derivatives as drug delivery systems for viral infection
Authors: Faghihkhorasani Amirhosein , Ahmed Hanan Hassan , Mashool Noor Muhammad , Alwan Mariem , Assefi Marjan , Adab Aya Hussein , Yasamineh Saman , Gholizadeh Omid , Baghani Moein
Published: October 2023

Viral infections in humans are responsible for fatalities worldwide and contribute to the incidence of various human ailments. Controllable targeted medicine delivery against many illnesses, including viral infection, may be significantly aided by using bacteria and bacteria-derived products. They may accumulate in diseased tissues despite physical obstacles, where they can launch antiviral immunity. The ability to genetically and chemically modify them means that vaccinations against viral infections may be manufactured and delivered to affected tissues more safely and effectively. The objective of this study is to provide an overview of the latest advancements in the field of utilizing bacteria and bacterial derivatives as carriers for administering medication to treat viral diseases such as SARS-CoV-2, hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human papillomavirus, influenza, and Ebola virus.

Graphical Abstract
Artificial intelligence in diagnostic pathology
Authors: Shafi Saba , Parwani Anil V.
Published: October 2023

Digital pathology (DP) is being increasingly employed in cancer diagnostics, providing additional tools for faster, higher-quality, accurate diagnosis. The practice of diagnostic pathology has gone through a staggering transformation wherein new tools such as digital imaging, advanced artificial intelligence (AI) algorithms, and computer-aided diagnostic techniques are being used for assisting, augmenting and empowering the computational histopathology and AI-enabled diagnostics. This is paving the way for advancement in precision medicine in cancer. Automated whole slide imaging (WSI) scanners are now rendering diagnostic quality, high-resolution images of entire glass slides and combining these images with innovative digital pathology tools is making it possible to integrate imaging into all aspects of pathology reporting including anatomical, clinical, and molecular pathology. The recent approvals of WSI scanners for primary diagnosis by the FDA as well as the approval of prostate AI algorithm has paved the way for starting to incorporate this exciting technology for use in primary diagnosis. AI tools can provide a unique platform for innovations and advances in anatomical and clinical pathology workflows. In this review, we describe the milestones and landmark trials in the use of AI in clinical pathology with emphasis on future directions.
Jejunal gastrointestinal stromal tumor that developed in a patient with neurofibromatosis type 1: a case report
Authors: Nagano Hideki , Ohyama Shigekazu , Sato Atsushi , Igarashi Jun , Yamamoto Tomoko , Kadoya Masumi , Kobayashi Mikiko
Published: October 2023

Background

Neurofibromatosis type 1 (NF1) is known to be associated with the frequent occurrence of unique gastrointestinal stromal tumors (GISTs), preferably occurring in the small intestine, with no mutations in the c-kit proto-oncogene or platelet-derived growth factor receptor-alpha (PDGFRA), with a high tendency for multifocal development, indolent nature, with low proliferation activity and favorable prognosis.

Case presentation

A woman in her forties visited her local doctor complaining of menstrual pain; a large mass was detected in her lower abdomen, and she was referred to our hospital. The patient had hundreds of skin warts and café au lait spots. The patient’s mother had been diagnosed with type 1 neurofibromatosis. The patient met the diagnostic criteria for NF1 and was diagnosed with NF1. Ultrasonography showed a large heterogeneous cystic mass with various echo patterns, solid compartments and multiple septations. Magnetic resonance imaging showed a multilocular cystic mass with liquid content exhibiting various intensities, including that of blood. A small round solid mass was also observed close to the cystic tumor. Contrast-enhanced computed tomography showed that the round solid mass showed strong enhancement in the early phase, unlike the cystic tumor component. Open laparotomy revealed a multicystic exophytic tumor measuring 11.5 cm originating from the jejunal wall, 20 cm distal to the duodenojejunal flexure. A solid tumor measuring 2.1 cm was also found on the anal side of the large tumor. We resected the short segment of the jejunum, including the two lesions. Microscopic findings revealed that the cystic and solid tumors consisted of spindle-shaped tumor cells showing little atypia with a fascicular or bundle arrangement. Nuclear mitosis was scarce. Immunostaining of the tumor cells showed positive staining for KIT and DOG1 and negative staining for S100 and desmin. The NF1 patient was diagnosed with multiple GISTs accompanied by intratumoral hemorrhagic denaturation arising from the jejunum. The TNM staging was pT4N0M0, stage IIIA.

Conclusion

We report a case of GISTs associated with NF1 that showed a jejunal origin, multifocal development and few mitotic figures. The recurrence risk, survival prognosis and need for adjuvant chemotherapy, particularly in cases where the initial GIST exhibits a very indolent pathology in NF1-related GISTs, remain to be elucidated.
Risk factors and healthcare costs associated with long bone fracture non-union: a retrospective US claims database analysis
Authors: Vanderkarr Mari F. , Ruppenkamp Jill W. , Vanderkarr Mollie , Holy Chantal E. , Blauth Michael
Published: October 2023

Background

Few contemporary US-based long bone non-union analyses have recently been published. Our study was designed to provide a current understanding of non-union risks and costs, from the payers' perspective.

Methods

The Merative™ MarketScan® Commercial Claims and Encounters database was used. Patients with surgically treated long bone (femur, tibia, or humerus) fractures in the inpatient setting, from Q4 2015 to most recent, were identified. Exclusion criteria included polytrauma and amputation at index. The primary outcome was a diagnosis of non-union in the 12 and 24 months post-index. Additional outcomes included concurrent infection, reoperation, and total healthcare costs. Age, gender, comorbidities, fracture characteristics, and severity were identified for all patients. Descriptive analyses were performed. Crude and adjusted rates of non-union (using Poisson regressions with log link) were calculated. Marginal incremental cost of care associated with non-union and infected non-union and reoperation were estimated using a generalized linear model with log link and gamma distribution.

Results

A total of 12,770, 13,504, and 4,805 patients with femoral, tibial, or humeral surgically treated fractures were identified, 74–89% were displaced, and 18–27% were comminuted. Two-year rates of non-union reached 8.5% (8.0%–9.1%), 9.1% (8.6%–9.7%), and 7.2% (6.4%–8.1%) in the femoral, tibial, and humeral fracture cohorts, respectively. Shaft fractures were at increased risk of non-union versus fractures in other sites (risk ratio (RR) in shaft fractures of the femur: 2.36 (1.81–3.04); tibia: 1.95 (1.47–2.57); humerus: 2.02 (1.42–2.87)). Fractures with severe soft tissue trauma (open vs. closed, Gustilo III vs. Gustilo I–II) were also at increased risk for non-union (RR for Gustilo III fracture (vs. closed) for femur: R = 1.96 (1.45–2.58), for tibia: 3.33 (2.85–3.87), RR for open (vs. closed) for humerus: 1.74 (1.30–2.32)). For all fractures, younger patients had a reduced risk of non-union compared to older patients. For tibial fractures, increasing comorbidity (Elixhauser Index 5 or greater) was associated with an increased risk of non-union. The two-year marginal cost of non-union ranged from $33K-$45K. Non-union reoperation added $16K–$34K in incremental costs. Concurrent infection further increased costs by $46K–$86K.

Conclusions

Non-union affects 7–10% of surgically treated long bone fracture cases. Shaft and complex fractures were at increased risk for non-union.
Healthcare workers’ experiences of workplace violence: a qualitative study in Lebanon
Authors: Abou-Abbas Linda , Nasrallah Rana , Yaacoub Sally , Yohana Ramirez Mendoza Jessica , Al Wais Mahmoud
Published: October 2023

Background

The COVID-19 pandemic has brought unprecedented challenges to healthcare workers (HCWs) around the world. The healthcare system in Lebanon was already under pressure due to economic instability and political unrest before the pandemic. This study aims to explore the impact of COVID-19 and the economic crisis on HCWs’ experiences of workplace violence in Lebanon.

Methods

A qualitative research design with an inductive approach was employed to gather data on workplace violence through Focus Group Discussions (FGDs) from HCWs in Tripoli Governmental Hospital (TGH), a governmental hospital in North Lebanon. Participants were recruited through purposive sampling. The interviews were conducted in Arabic, recorded, transcribed, and translated into English. Thematic analysis was used to analyze the data.

Results

A total of 27 employees at the hospital participated in the six FGDs, of which 15 females and 12 males. The analysis identified four main themes: (1) Types of violence, (2) Events witnessed, (3) Staff reactions to violence, and (4) Causes of violence. According to the interviews conducted, all the staff members, whether they had experienced or witnessed violent behavior, reported that such incidents occurred frequently, ranging from verbal abuse to physical assault, and sometimes even involving the use of weapons. The study findings suggest that several factors contribute to the prevalence of violence in TGH, including patients’ financial status, cultural beliefs, and lack of medical knowledge. The hospital’s location in an area with a culture of nepotism and favoritism further exacerbates the issue. The staff’s collective response to dealing with violence is either to submit to the aggressor’s demands or to remove themselves from the situation by running away. Participants reported an increase in workplace violence during the COVID-19 pandemic and the exacerbated economic crisis in Lebanon and the pandemic.

Conclusion

Interventions at different levels, such as logistical, policy, and education interventions, can help prevent and address workplace violence. Community-level interventions, such as raising awareness and engaging with non-state armed groups, are also essential to promoting a culture of respect and zero tolerance for violence.
Effectiveness and safety of digital rectal stimulation and abdominal massage for neurogenic bowel dysfunction in stroke patients: a randomized controlled trial protocol
Authors: Ma Sumin , Fan Xiaoyan , He Ying , Li Chengjuan , Qu Dandan , Man Yanli
Published: October 2023

Background

Neurogenic bowel dysfunction (NBD) is a prevalent complication among stroke patients, significantly affecting their quality of life, duration of hospitalization, medical expenses, and even mortality. Although current guidelines suggest a conservative strategy for addressing bowel dysfunction, which includes techniques such as digital rectal stimulation (DRS) and abdominal massage, the availability of interventions remains limited in healthcare facilities.

Methods

This study follows a prospective randomized controlled parallel-group clinical trial design. The control group will receive standard care, while the intervention group will undergo a program that combines DRS and abdominal massage in addition to standard care. The duration of the intervention for both groups will be 6 weeks. The primary outcome measures will be the Wexner score. Furthermore, secondary outcomes measure will be assessed, including Bristol score, Patient Assessment of Constipation-Quality of Life (PAC-QoL), and Fecal Incontinence Quality of Life (FI-QoL).

Discussion

This study aims to evaluate the effectiveness and safety of a bowel rehabilitation program for stroke patients with NBD. The findings will provide information that can contribute to the formulation of bowel management strategies.

Trial registration

The study has been registered in the Chinese Clinical Registry under the number ChiCTR2300071709. This registration was completed on May 23, 2023. All items from the World Health Organization Trial Registration Data set are described in this manuscript.
First field and laboratory evaluation of LAMP assay for malaria diagnosis in Cubal, Angola
Authors: Febrer-Sendra Begoña , Crego-Vicente Beatriz , Nindia Arlette , Martínez-Campreciós Joan , Aixut Sandra , Mediavilla Alejandro , Silgado Aroa , Oliveira-Souto Inés , Salvador Fernando , Molina Israel , Muro Antonio , Sulleiro Elena , Fernández-Soto Pedro
Published: October 2023

Background

Malaria is a globally distributed infectious disease. According to the World Health Organization, Angola is one of the six countries that account for over half the global malaria burden in terms of both malaria cases and deaths. Diagnosis of malaria still depends on microscopic examination of thin and thick blood smears and rapid diagnostic tests (RDTs), which often lack analytical and clinical sensitivity. Molecular methods could overcome these disadvantages. The aim of this study was to evaluate, for the first time to our knowledge, the performance of a loop-mediated isothermal amplification (LAMP) for the diagnosis of malaria in an endemic area in Cubal, Angola, and to assess the reproducibility at a reference laboratory.

Methods

A total of 200 blood samples from patients attended at Hospital Nossa Senhora da Paz, Cubal, Angola, were analysed for Plasmodium spp. detection by microscopy, RDTs, and LAMP. LAMP assay was easily performed in a portable heating block, and the results were visualized by a simple colour change. Subsequently, the samples were sent to a reference laboratory in Spain to be reanalysed by the same colorimetric LAMP assay and also in real-time LAMP format.

Results

In field tests, a total of 67/200 (33.5%) blood samples were microscopy-positive for Plasmodium spp., 98/200 RDT positive, and 112/200 (56%) LAMP positive. Using microscopy as reference standard, field LAMP detected more microscopy-positive samples than RDTs (66/67; 98% vs. 62/67; 92.5%). When samples were reanalysed at a reference laboratory in Spain using both colorimetric and real-time assays, the overall reproducibility achieved 84.5%.

Conclusions

This is the first study to our knowledge in which LAMP has been clinically evaluated on blood samples in a resource-poor malaria-endemic area. The colorimetric LAMP proved to be more sensitive than microscopy and RDTs for malaria diagnosis in field conditions. Furthermore, LAMP showed an acceptable level of reproducibility in a reference laboratory. The possibility to use LAMP in a real-time format in a portable device reinforces the reliability of the assay for molecular diagnosis of malaria in resource-poor laboratories in endemic areas.

Graphical Abstract
Sub-lethal exposure to chlorfenapyr reduces the probability of developing Plasmodium falciparum parasites in surviving Anopheles mosquitoes
Authors: Kweyamba Prisca A. , Hofer Lorenz M. , Kibondo Ummi A. , Mwanga Rehema Y. , Sayi Rajabu M. , Matwewe Fatuma , Austin James W. , Stutz Susanne , Moore Sarah J. , Müller Pie , Tambwe Mgeni M.
Published: October 2023

Background

Pyrethroid resistance in the key malaria vectors threatens the success of pyrethroid-treated nets. To overcome pyrethroid resistance, Interceptor® G2 (IG2), a ‘first-in-class’ dual insecticidal net that combines alpha-cypermethrin with chlorfenapyr, was developed. Chlorfenapyr is a pro-insecticide, requiring bio-activation by oxidative metabolism within the insect’s mitochondria, constituting a mode of action preventing cross-resistance to pyrethroids. Recent epidemiological trials conducted in Benin and Tanzania confirm IG2’s public health value in areas with pyrethroid-resistant Anopheles mosquitoes. As chlorfenapyr might also interfere with the metabolic mechanism of the Plasmodium parasite, we hypothesised that chlorfenapyr may provide additional transmission-reducing effects even if a mosquito survives a sub-lethal dose.

Methods

We tested the effect of chlorfenapyr netting to reduce Plasmodium falciparum transmission using a modified WHO tunnel test with a dose yielding sub-lethal effects. Pyrethroid-resistant Anopheles gambiae s.s. with L1014F and L1014S knockdown resistance alleles and expression levels of pyrethroid metabolisers CYP6P3, CYP6M2, CYP4G16 and CYP6P1 confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) prior to conducting experiments were exposed to untreated netting and netting treated with 200 mg/m3 chlorfenapyr for 8 h overnight and then fed on gametocytemic blood meals from naturally infected individuals. Prevalence and intensity of oocysts and sporozoites were determined on day 8 and day 16 after feeding.

Results

Both prevalence and intensity of P. falciparum infection in the surviving mosquitoes were substantially reduced in the chlorfenapyr-exposed mosquitoes compared to untreated nets. The odds ratios in the prevalence of oocysts and sporozoites were 0.33 (95% confidence interval; 95% CI 0.23–0.46) and 0.43 (95% CI 0.25–0.73), respectively, while only the incidence rate ratio for oocysts was 0.30 (95% CI 0.22–0.41).

Conclusion

We demonstrated that sub-lethal exposure of pyrethroid-resistant mosquitoes to chlorfenapyr substantially reduces the proportion of infected mosquitoes and the intensity of the P. falciparum infection. This will likely also contribute to the reduction of malaria in communities beyond the direct killing of mosquitoes.

Graphical Abstract
Abscess pulsatility: a sonographic sign of osteomyelitis
Authors: Werenski Hope , Ford Kristy , Casey Dillon , Glass Casey , Schoeneck Jacob
Published: October 2023

Introduction

Early diagnosis and aggressive treatment of acute osteomyelitis may improve prognosis and prevent further complications. Sonography is useful in the evaluation of osteomyelitis. It can demonstrate early signs of inflammation, such as soft tissue changes near the affected bone, periosteal thickening, periosteal elevation, and subperiosteal abscess.

Case presentation

A 68-year-old female presented to the emergency department with 3 weeks of worsening left lower extremity pain. She was initially seen by urgent care for left shin erythema and swelling and treated for cellulitis with intramuscular ceftriaxone without improvement. On presentation, she was afebrile and hemodynamically stable with erythema, swelling, and tenderness of the left pretibial soft tissues. Her labs revealed leukocytosis and elevated inflammatory markers. Point-of-care ultrasound demonstrated a bidirectional flow of fluid through a disruption in the bone cortex visualized on greyscale imaging and confirmed with color and spectral Doppler. The patient was diagnosed with osteomyelitis and treated with antibiotics and incision and drainage by orthopedic surgery.

Discussion

The unique sonographic finding of pulsatile flow of fluid within an abscess near bone has not been previously described in the literature. The presence of Doppler signal in any fluid other than blood is known as pseudoflow. The presence of pulsatility in this case, which could represent either blood or pseudoflow, drew the ultrasound operator's eye to the cortical defect and lead to the diagnosis of osteomyelitis.

Conclusions

The sonographic finding of pulsatility in an abscess near bone should raise the concern for communication with the medullary cavity.
Histiocytic sarcoma in renal transplant patients: a literature review
Authors: Salehi Mahsa , Rehman Shafi , Qutab Miraa , Altheeb Ruba , Prakash Rashmi , Jafari Hamid Reza
Published: October 2023

Background

Histiocytic sarcoma (HS) is defined as neoplasm resembling morphological and immunophenotypic characteristics of mature histiocytes. It is a rare form of lymphoid neoplasms. Despite advances in treatment and diagnosis of histiocytic sarcoma, majority of cases had poor prognosis due to progressive nature of the disease. In the following article, all reported cases of histiocytic sarcoma in renal transplant patients are reviewed.

Methods

In our literature review, all relevant reports were collected electronically by entering the necessary keywords. A Boolean approach using Medical Subject Heading (MeSH) keywords was implemented. After establishing the inclusion/exclusion criteria, article titles and abstracts were evaluated by Systematic Reviews and Meta-Analyses (PRISMA) standards for 2020. All cases of histiocytic sarcoma in renal transplant patients were included.

Result

Based on our inclusion and exclusion criteria 4 case reports were yielded in this review. Two were males and 2 were females with the mean age of 42.25 years. Fever was the most common symptom. Although tumor originated from the native kidney on one patient, the site of the primary tumor was thorax, oropharynx, and transplanted kidney in the rest. Metastasis was detected in all cases. Prednisone was used for all cases. EBV was positive in 2 cases and negative in one of them. Histology was diagnostic and similar in all cases. Immunohistochemistry was done for 3 cases. Although chemotherapy was done for 3 patients, all 4 cases ended in mortality.

Conclusion

Despite the fact that neoplasms are post renal transplant complications, histiocytic sarcoma is a scarce and fatal entity in such patients. Histological and immunohistochemistry tests are the corner stone in diagnosis of histiocytic sarcoma.
The student patient alliance: development and formative evaluation of an initiative to support collaborations between patient and public involvement partners and doctoral students
Authors: Simons Gwenda , Birch Rebecca , Stocks Joanne , Insch Elspeth , Rijckborst Rob , Neag Georgiana , McColm Heidi , Romaniuk Leigh , Wright Claire , Phillips Bethan E. , Jones Simon W. , Pratt Arthur G. , Siebert Stefan , Raza Karim , Falahee Marie
Published: October 2023

Background

While the integration of patient and public involvement (PPI) in clinical research is now widespread and recommended as standard practice, meaningful PPI in pre-clinical, discovery science research is more difficult to achieve. One potential way to address this is by integrating PPI into the training programmes of discovery science postgraduate doctoral students. This paper describes the development and formative evaluation of the Student Patient Alliance (SPA), a programme developed at the University of Birmingham that connects PPI partners with doctoral students.

Methods

Following a successful pilot of the SPA by the Rheumatology Research Group at the University of Birmingham, the scheme was implemented across several collaborating Versus Arthritis / Medical Research Council (MRC) centres of excellence. Doctoral students were partnered with PPI partners, provided with initial information and guidance, and then encouraged to work together on research and public engagement activities. After six months, students, their PPI partners and the PPI coordinators at each centre completed brief surveys about their participation in the SPA.

Results

Both doctoral students and their PPI partners felt that taking part in SPA had a positive impact on understanding, motivation and communication skills. Students reported an increased understanding of PPI and patient priorities and reported improved public engagement skills. Their PPI partners reported a positive impact of the collaboration with the students. They enjoyed learning about the student’s research and contributing to the student’s personal development. PPI coordinators also highlighted the benefits of the SPA, but noted some challenges they had experienced, such as difficulties matching students with PPI partners.

Conclusions

The SPA was valued by students and PPI partners, and it is likely that initiatives of this kind would enhance students’ PPI and public engagement skills and awareness of patients’ experiences on a wider scale. However, appropriate resources are needed at an institutional level to support the implementation of effective programmes of this kind on a larger scale.
Validation of the six-minute walking distance measured by FeetMe® insoles
Authors: Mostovov Andrey , Jacobs Damien , Farid Leila , Dhellin Paul , Baille Guillaume
Published: October 2023

Background

The six-minute walk test (6MWT) is widely used to assess functional capacity in patients with various diseases. Use of wearable devices can make this test more accurate and easier to administer, and may even enhance it by providing additional information. The purpose of this study was to evaluate the validity of FeetMe® insoles for assessing the total six-minute walking distance (6MWD) by comparing the FeetMe® estimates and those obtained by a rater to the ground truth measured with a surveyor’s wheel.

Results

Data were analyzed from healthy volunteers who performed the 6MWT on 10-m and 30-m tracks while wearing FeetMe® insoles (n = 32), and being simultaneously assessed by a rater (n = 33) and followed by an investigator with a surveyor’s wheel. The mean average error (MAE) of the estimates was below 13 m on both tracks for FeetMe®, whereas it ranged from 16.24 m to 38.88 m on the 30-m and 10-m tracks for the rater.

Conclusion

The FeetMe® insoles provided a more accurate estimate and showed greater agreement with the ground truth than the rater, and the accuracy of the FeetMe® estimates did not vary according to the track length. We conclude that the FeetMe insoles are a valid solution for measuring the 6MWD.
Feasibility of Weekly Electronic Health Record–Embedded Patient-Reported Outcomes for Patients Starting Oral Cancer–Directed Therapy
Authors: Doolin Jim W. , Haakenstad Ellana K. , Neville Bridget A. , Lipsitz Stu R. , Zhang Sunyi , Cleveland Jessica L.F. , Hiruy Semegne , Hassett Michael J. , Revette Anna , Schrag Deborah , Basch Ethan , McCleary Nadine J.
Published: October 2023

DFCI feasibility study shows patients on oral anticancer Rx's use EHR-embedded ePROs, but there is room to improve.
lncRNA Hnscr Regulates Lipid Metabolism by Mediating Adipocyte Lipolysis
Authors: Guo Yi-Fan , Sun Jing-Yi , Liu Ya , Liu Zhe-Yu , Huang Yan , Xiao Yuan , Su Tian
Published: October 2023

Obesity is a process of fat accumulation due to the imbalance between energy intake and consumption. Long noncoding RNA (lncRNA) Hnscr is crucial for metabolic regulation, but its roles in lipid metabolism during obesity are still unknown. In this article, we found that the expression of Hnscr gradually decreased in adipose tissues of diet-induced obese mice. Furthermore, the deletion of Hnscr promoted an increase in body weight and adipose tissue weight by upregulating the expression of lipogenesis genes and downregulating lipolysis genes in inguinal white adipose tissue (iWAT) and brown adipose tissue. In vitro knockdown of Hnscr in adipocytes resulted in reduced lipolysis of adipocytes. Overexpression of Hnscr by adenovirus or drug mimics showed the opposite. Mechanistically, Hnscr regulated adipose lipid metabolism by mediating the cyclic adenosine monophosphate/protein kinase A signaling pathway. This study identifies the initial characterization of Hnscr as a critical modifier that regulates lipid metabolism, suggesting that lncRNA Hnscr is a potential target for treating obesity.
Study of the Villafranchian large mammal fauna from Karnezeika (Argolis, Peloponnese, Greece)
Authors: Σιάνης Παναγιώτης-Δημήτριος
Published: October 2023

Η θέση Καρνεζέικα βρίσκεται στο νότιο τμήμα του νομού Αργολίδας και αντιστοιχείστο Κατώτερο Πλειστόκαινο. Αποτελεί μια μικρή δολίνη σχηματισμένη στα ανθρακικά πετρώματατου υποστρώματος ηλικίας Ανώτερου Τριασικού / Κατώτερου Ιουρασικού του Σχηματισμού τουΠαντοκράτορα της Πελαγονικής ζώνης. Πιθανότατα η θέση λειτούργησε ως φυσική παγίδα η οποίασταδιακά γέμισε με ιζήματα, πετρώματα και κυρίως σκελετικό υλικό θηλαστικών από την ευρύτερηπεριοχή, που μεταφέρθηκε εκεί από τις ενέργειες του νερού και της βαρύτητας, δημιουργώντας έτσιευνοϊκές συνθήκες για την απολίθωσή τους. Η μεγάλη συλλογή απολιθωμάτων θηλαστικών από ταΚαρνεζέικα είναι το αντικείμενο της τρέχουσας διδακτορικής μελέτης.Συνολικά, έχουν καταγραφεί 3358 αναγνωρίσιμα δείγματα. Εκτός από αυτά, υπάρχουν επίσηςπερισσότερα από 7000 καταγεγραμμένα δείγματα πολύ μικρών θραυσμάτων κάθε είδους οστών. Ομεγάλος αριθμός κατακερματισμένου υλικού δείχνει ότι τα περισσότερα από αυτά μεταφέρθηκανμάλλον βίαια στον τελικό τόπο ταφής και η μεταφορά φαίνεται να ήταν αρκετά γρήγορη αφού ταοστά δεν παρουσιάζουν ιδιαίτερα σημάδια φθοράς ή τριβής. Δεν καταγράφηκαν ίχνηδραστηριότητας σαρκοφάγων. Όλα αυτά, σε συνδυασμό με την παρουσία οστών με διάφορες τιμέςτου Fluvial Transport Index, καθώς και την έλλειψη αρθρωτών στοιχείων και οποιοδήποτε σημάδιβιοκλαστικής ταξινόμησης, δείχνει ότι ο τόπος θανάτου ήταν περιφερειακός της δολίνης και ταοστά μεταφέρθηκαν από περιοχή σε κοντινή απόσταση και γύρω από αυτή.Η μεγάλη πανίδα των θηλαστικών που προσδιορίστηκε, κυριαρχείται σε μεγάλο βαθμό απόβοοειδή συμπεριλαμβανομένων των Gazella bouvrainae, Gazellospira torticornis, Gallogoralmeneghinii και Caprini gen. et sp. indet.. Αυτό είναι ένα αρκετά ασυνήθιστο χαρακτηριστικό για τιςμετα-Πλειοκαινικές ελληνικές θέσεις, όπου γενικά εμφανίζεται μεγάλος αριθμός δειγμάτωνιπποειδών. Εκτός από τέσσερα είδη βοοειδών και ένα ιπποειδές, προσδιορίστηκαν επίσης τρίαδιαφορετικά είδη ελαφιών, η καμηλοπάρδαλη Palaeotragus inexpectatus, ο ρινόκεροςStephanorhinus etruscus, επτά διαφορετικά σαρκοφάγα, καθώς και υπολείμματα ενός σπάνιουμεγάλου cercopithecid, καθιστώντας τα Καρνεζέικα ως μία από τις θέσεις με παρουσίαπρωτεύοντος στο Πλειστόκαινο της Ευρώπης.Η παρουσία των βοοειδών G. bouvrainae – G. meneghinii – G. torticornis, σε συνδυασμό μετα τρία ελάφια, είναι χαρακτηριστικά της πανίδας του Μέσου Βιλλαφράγκιου της Ελλάδας (2,6 –1,8 Ma). Επιπροσθέτως, ενδιαφέρον παρουσιάζει και η παρουσία πολυάριθμων ατόμων G.meneghinii, ένα είδος που συνήθως αποτελεί ένα αρκετά σπάνιο στοιχείο στο ελληνικό αρχείοαπολιθωμάτων. Επιπλέον, το σύνολο περιέχει πολλά σαρκοφάγα και αρτιοδάκτυλα πουεκπροσωπούν μικτά ενδιαιτήματα. Αυτές οι παρατηρήσεις, σε συνδυασμό με την εξαιρετικά φτωχήπαρουσία ιπποειδών, τα οποία αντιπροσωπεύονται από ελάχιστα δείγματα και την απουσία τυπικώναρπακτικών ανοιχτού περιβάλλοντος, πιθανότατα δείχνουν ότι το παλαιοπεριβάλλον της θέσηςΚαρνεζέικα αντιπροσωπευόταν από βραχώδη ασβεστολιθικά υπόβαθρα με λόφους και πλαγιές.
Ο ρόλος των Micro-RNAs στους στρωματικούς όγκους του γαστρεντερικού συστήματος
Authors: Στεφάνου Ιωάννης
Published: October 2023

Η παρούσα διδακτορική διατριβή αποτελεί μια αναδρομική κλινικοεργαστηριακή μελέτη, στην οποία διερευνήσαμε τα πρότυπα έκφρασης των micro-RNAs σε δείγματα ιστών που αφορούσαν γαστρικούς όγκους στομάχου σε σύγκριση με μη νεοπλασματικούς γαστρικούς ιστούς. Εκτός της ανάλυσης των miRNAs με την μηχανή ανίχνευσης RNA αλληλουχιών νέας γενιάς, εφαρμόσαμε αλγοριθμικά μοντέλα μηχανικής εκμάθησης (machine learning models) με σκοπό να αναδείξουμε τα σημαντικότερα miRNAs ως προγνωστικούς δείκτες κακοήθειας. Οι νεοπλασματικοί ιστοί που μελετήθηκαν αφορούν χειρουργικές εκτομές στρωματικών όγκων στομάχου, ενώ οι υγιείς αντιστοιχούν σε βιοψίες από ενδοσκοπήσεις ανωτέρου πεπτικού για καλοήθεις παθήσεις. Τα στοιχεία των ασθενών συλλέχθηκαν από το αρχείο του Γ.Ν.Ιπποκρατείου Αθηνών και η διεξαγωγή του εργαστηριακού τμήματος της μελέτης πραγματοποιήθηκε στο Εργαστήριο Βιολογίας Ιατρικής Σχολής του Πανεπιστημίου Αθηνών.Για τα περισσότερα από τα miRNA που βρήκαμε να έχουν στατιστικά σημαντική διαφοροποίηση στην έκφρασή τους (GISTs vs Controls), είχε περιγραφεί η συσχέτισή τους με τα GIST σε προηγηθείσες μελέτες. Πιο συγκεκριμένα βρήκαμε ότι τα hsa-miR-196a-5p, hsamiR-148a-3p and hsamiR-125a-5p υπερεκφράζονται στα GIST, ενώ τα hsamiR- let-7f-5p, hsamiR- 126-3p, hsa-miR-222-3p, hsa-miR-146a-5p, hsa-miR- 218-5p μεταξύ άλλων, εμφανίζουν μειωμένη έκφραση. Τα αποτελέσματα της μελέτης μας υποδηλώνουν ότι τα εν λόγω miRNAs θα μπορούσαν να χρησιμεύσουν ως προγνωστικοί δείκτες για την ανάπτυξη των GISTs.
Ανοσοβιολογικές ενδείξεις για το ρόλο της δεαμινάσης της κυτιδίνης στην οντογένεση της χρόνιας λεμφοκυτταρικής λευχαιμίας
Authors: Σοφού Ηλέκτρα
Published: October 2023

Η ανοσογενετική ανάλυση των ανοσοσφαιρινών του Β κυταρικού υποδοχέα (ΒκΥ) στη χρόνια λεμφοκυτταρική λευχαιμία (ΧΛΛ) έχει συμβάλλει καθοριστικά στην καλύτερη κατανόηση της βιολογίας της νόσου και στην καλύτερη διαχείριση των ασθενών. Κομβικά ευρήματα προς αυτή την κατεύθυνση υπήρξαν η ανακάλυψη ότι το φορτίο σωματικής υπερμεταλλαξιγένεσης μπορεί να διακρίνει τους ασθενείς με ΧΛΛ σε δύο μεγάλες ομάδες με διακριτή κλινική συμπεριφορά και ότι 41% των ασθενών κατατάσσονται σε μικρότερες ομάδες με βάση τα ανοσογενετικά χαρακτηριστικά του ΒκΥ. Παρότι αυτά τα ευρήματα έχουν σημαντικές προεκτάσεις για την οντογένεση της νόσου, το κύτταρο προέλευσης της ΧΛΛ παραμένει ακόμα άγνωστο. Διαφορετικές δημοσιευμένες μελέτες επικεντρώθηκαν στο ρόλο της δεαμινάσης της κυτιδίνης (AID) στην οντογένεση της ΧΛΛ, ιδίως λόγω του ρόλου της στην ενεργοποίηση των μηχανισμών της σωματικής υπερμεταλλαξιγένεσης (ΣΥΜ) και εναλλαγής ισοτύπου που είναι καθοριστικής σημασίας στη Β λεμφική σειρά. Ωστόσο, οι μελέτες αυτές παρουσίαζαν εγγενείς περιορισμούς λόγω των μεθοδολογιών μικρής κλίμακας που χρησιμοποίησαν. Στην παρούσα διδακτορική διατριβή εφαρμόστηκε λειτουργική ανοσογενετική ανάλυση μεγάλης κλίμακας με σκοπό την επανεξέταση του ρόλου της AID στην οντογένεση της ΧΛΛ. Τα αποτελέσματα της μελέτης αναδεικνύουν διαφορική δράση της AID μεταξύ Α-ΧΛΛ και Μ-ΧΛΛ, η οποία αντικατοπτρίζεται και στην αρχιτεκτονική των ρεπερτορίων των ΧΛΛ κλώνων των αντίστοιχων ασθενών, ιδίως στην περίπτωση της Α-ΧΛΛ. Συγκεκριμένα, οι ασθενείς της κατηγορίας Α-ΧΛΛ βρέθηκαν να παρουσιάζουν ιδιαίτερα πολύπλοκη υποκλωνική αρχιτεκτονική τόσο in vivo όσο και in vitro, η οποία χαρακτηρίζεται από συχνά και ευρείας κλίμακας φαινόμενα εναλλαγής ισοτύπου και σωματικής υπερμεταλλαξιγένεσης ακόμα και στην υπερμεταβλητή περιοχή VH CDR3. Συνολικά, τα ευρήματα της παρούσας μελέτης αναδεικνύουν τη δυναμική φύση του ρεπερτορίου των Β λεμφοκυττάρων στις διαφορετικές ομάδες ΧΛΛ, με σημαντικές οντογενετικές προεκτάσεις ιδίως υπό το πρίσμα του χρονικού πλαισίου μέσα στο οποίο δρα η AID για να διεκπεραιώσει την ωρίμανση συγγένειας του ΒκΥ.
Impressions of science and healthcare professionals who share anti-science conspiracy theories
Authors: Green Ricky , Toribio-Flórez Daniel , Douglas Karen M.
Published: October 2023

Background: The majority of science and healthcare professionals agree with the scientific consensus on issues such as anthropogenic climate change and the safety and efficacy of vaccines. However, a small number of professionals diverge from this consensus and espouse conspiracy theories arguing, for example, that climate change is a hoax and that the dangers of vaccines are being hidden by greedy pharmaceutical companies. What impressions do people make of conspiracy-sharing professionals and, importantly, would people follow their advice? We aimed to answer these questions in a brief report comprising of two preregistered experiments.

Methods: In Experiment 1 (N = 296) participants rated their impressions of a scientist who endorsed (vs. refuted) climate change conspiracy theories, and indicated their willingness to follow the scientist’s advice. Experiment 2 (N = 280) followed a similar method but focused on a healthcare professional who endorsed (vs. refuted) mRNA vaccine conspiracy theories. In a control condition, the professional provided neutral information.

Results: In both experiments, people formed negative impressions of the conspiracy-sharing professional, perceiving them to be less trustworthy, honest, brave (Experiment 1 only), credible, intelligent, less able to effect change, and more of an outsider and a fraud. They also showed less willingness to follow the professionals’ advice. However, participants’ own conspiracy beliefs shaped these impressions, with stronger negative impressions found among participants with weaker conspiracy beliefs. Notably, higher conspiracy believers perceived the conspiracy-sharing professionals as braver.

Conclusions: These findings suggest that scientific and healthcare professionals who share conspiracy theories are perceived negatively, and people are less willing to follow advice. However, this is moderated by participants’ own conspiracy beliefs.
Risk identification in managing small and medium-sized enterprises in Poland
Authors: Kokot-Stępień Patrycja
Published: October 2023

Motivation: When running a business in the form of an enterprise, we agree to take the associated risk. The ubiquitous uncertainty about the future of enterprises, especially from the SME sector, makes risk management more and more important, which includes several successive stages. One of the most important is risk identification. Its purpose is relatively early detection of possible threats that, if they occur, will affect the company and its goals. Knowledge of the factors that may disrupt the functioning of an entity, especially a small and medium one, is the foundation in the approach to the issue of risk accompanying business activity. Properly conducted risk identification should cover all levels of the company’s operation and its relations with the environment.Aim: The article will isolate events, the occurrence of which small and medium-sized entrepreneurs fear the most. The aim of this article is to develop a register of risk sources for SMEs, and to identify the risks that pose the greatest threat to the operation of SMEs. Moreover, the level of individual sources of risk will be assessed allowing to identify the key disruptors for the operation of SME’s. The relationship between the level of risk and the size of the entity will also be examined.Results: Identification of factors threatening the functioning of enterprises increases the effectiveness of risk management that accompanies the conducted activity. Empirical research allowed to recognize the most important categories and the main sources of risk associated with SME activities. The dependency between risk categories and the size of the business was confirmed, with the strength of this relationship being moderate at best.