bluuebunny/crossref_metadata_2025 huggingface dataset:
An update on corticosteroid treatment for IgA nephropathy
Authors: Ghaddar Malak , Barratt Jonathan , Barbour Sean J.
Published: March 2023

Purpose of review

The use of corticosteroids to treat IgA nephropathy (IgAN) has been limited by many controversies related to uncertain benefit and safety concerns. Recent trials have tried to address these limitations.

Recent findings

After being paused because of an excess of adverse events in the full-dose steroid arm, the TESTING trial compared a reduced dose of methylprednisolone to placebo in patients with IgAN after optimization of supportive therapy. Steroid treatment was associated with a significant reduction in the risk of a 40% decline in estimated glomerular filtration rate (eGFR), kidney failure and kidney death as well as a sustained decrease in proteinuria compared with placebo. Serious adverse events were more frequent with the full dose regimen but less common in the reduced dose regimen. A phase III trial evaluating a new formulation of targeted-release budesonide showed a significant reduction in short-term proteinuria and has resulted in accelerated FDA approval for use in the United States. In a subgroup analysis of DAPA-CKD trial, sodium-glucose transport protein 2 inhibitors reduced the risk of kidney function decline in patients who have completed or are not eligible for immunosuppression.

Both reduced-dose corticosteroids and targeted-release budesonide are new therapeutic options that can be used in patients with high-risk disease. More novel-targeted therapies with a better safety profile are currently under investigations.
Methods to assess the effectiveness and acceptance of information and communication technology-based assistive technology for older adults: a scoping review
Authors: Tónay Gabriella , Pilissy Tamás , Tóth András , Fazekas Gábor
Published: March 2023

An aging society is a growing challenge for families, social and rehabilitation service providers, and economies. Information and communication technology-based assistive technology can bolster the independence of older adults (65 years and above) and reduce their burden on caregivers. Currently, there is no unified methodology to assess the effectiveness and acceptance of these technologies. The present study undertakes a scoping review to (1) identify and characterize the methods for assessing the acceptability and usability of information and communication technology-based assistive technologies, (2) explore the advantages and disadvantages of the assessment methods, (3) determine the possibilities of combining the assessment methods and (4) define the most commonly used assessment method and set of outcome measures. The literature was searched in MEDLINE, Scopus, IEEE Cochrane and Web of Science bibliographic databases using the keywords defined by reviewers for articles in English published between 2011 and 2021. Of the 1696 matches, 31 met the inclusion criteria. It was found that a combination of different assessment methods was common in outcome measurements. Of the 31 studies, assessment methods were combined in 21 studies and multiple questionnaires were used in 11 studies. The most common technique of outcome measurement was the use of questionnaires (81%), conducting interviews (48%) and recording usability-performance measures (39%). The advantages and disadvantages of the assessment methods could not be determined in the selected studies in this scoping review.
Pontine and bilateral cerebellar lesion in osmotic demyelination syndrome associated with uncontrolled type II diabetes mellitus: a case report
Authors: Shrestha Suraj , Kharel Sanjeev , Gautam Sandesh , Poddar Elisha , Adhikari Sugat , Acharya Suman , Pant Samriddha Raj , Jha Anamika , Ojha Rajeev
Published: March 2023

Introduction and importance:

Osmotic demyelination syndrome (ODS) as a result of the hyperosmolar hyperglycemic state is rare and can present with variable neurological manifestation due to lysis of myelin sheath.

Case presentation:

A 44-year diabetic male presented with complaints of sudden onset, progressive bilateral weakness in lower limbs, and slurring of speech for the past 1.5 months. Cerebellar examination showed a bilaterally impaired finger nose test, dysdiadochokinesia, impaired heel shin test, and an impaired tandem gait. MRI brain (T2 and fluid-attenuated inversion recovery sequences) showed high signal intensity in the central pons and bilateral cerebellum. With a diagnosis of ODS with poorly controlled diabetes, he was treated with insulin, metformin, and supportive measures following which his symptoms subsided gradually.

Clinical discussion:

A rapid correction of hyponatremia is considered the most common cause of ODS. Variations in plasma glucose levels, a rare cause of ODS, can cause an abrupt osmolality change causing pontine and extrapontine myelinolysis. Prevention of rapid correction of hyponatremia and rapid changes in plasma osmolality in vulnerable patients is the mainstay of treatment.

Conclusions:

Clinical features, imaging studies, and monitoring of serum osmolality, serum glucose, and electrolytes aid in diagnosis and favorable outcomes for the patient.
Partial Sheehan’s syndrome with abdominal tuberculosis presented with pancytopenia and fluctuating thyroid profile: a case report
Authors: Yadav Prashant , Bari Md Anwarul , Saha Akash , Yadav Sushmita , Khan Amzad H.
Published: March 2023

Introduction:

Sheehan’s syndrome is a well-recognized cause of panhypopituitarism secondary to pituitary apoplexy, followed by postpartum hemorrhage. Depending upon the degree of ischemic injury, it can be either partial or complete.

Case presentation:

We report an interesting case of a 35-year-old woman admitted to our hospital with complaints of abdominal distension, which was later presumed to be due to disseminated tuberculosis (TB) after excluding the possible differentials. During the treatment course, she was going through repeated attacks of hypovolemic shock and hypoglycemia due to adrenocortical insufficiency. This, along with the history of prolonged amenorrhea 4 years back due to severe postpartum hemorrhage in her last pregnancy, has led us to our diagnosis of partial Sheehan’s syndrome. After 1 month of starting steroid and anti-TB therapy, it was quite surprising when she presented with features of pancytopenia and antitubercular drug-induced hepatitis.

Discussion:

Sheehan’s syndrome may have a varying degree of presentation depending upon the degree of damage to the pituitary gland, which includes amenorrhea, lactation failure, adrenocortical insufficiency, hyponatremia, hypoglycemia, as well as pancytopenia in some rare instances The hormone panel especially the thyroid profile should be monitored carefully. Such cases are often challenging to deal with because of their varying degrees of presentation and the delay in diagnosis due to a lack of clinical suspicion.

Conclusion:

Therefore, we believe that this rare presentation of pancytopenia in Sheehan’s syndrome with fluctuating thyroid profile and abdominal TB in the background will let clinicians approach such a rare disease differently.
Idiopathic recurrent pyoderma gangrenosum with cobalamin deficiency in a 62-year-old male: a case report
Authors: Sitaula Seema , Kharel Sanjeev , Sherpali Aakash , Shrees Vijay , Mainali Atul
Published: March 2023

Introduction:

Pyoderma gangrenosum (PG) is a rare, neither infectious nor gangrenous, neutrophil-mediated inflammatory dermatosis. In 50–70% of cases, systemic disease is the underlying cause, and the remaining is idiopathic.

Case Presentation:

The authors here present a case of a 62-year-old male with a history of recurrent ulcer over the dorsum of hand diagnosed with recurrent PG with cobalamin deficiency treated with intralesional steroid injection and topical antibiotics along with intramuscular vitamin B12 injections. The patient returned after a year with a history of swelling in the left hand for 1 week, which was managed with intravenous antibiotics.

Clinical Discussion:

The most common kind of PG is ulcerative, which accounts for around 85% of cases that have been found. Ulcerative PG begins as small, painful erythematous or violaceous papules and pustules that quickly develop into ulcers with an exudative, mucopurulent, hemorrhagic base or with areas of necrosis and high, well-defined, serpiginous, violet-blue, or metallic grey borders, which are its defining feature. Glucocorticoids, along with a wide range of additional systemic immunomodulatory medication as alternatives and antibiotics to prevent infection are used for treatment.

Conclusion:

PG is a rare form of neutrophilic dermatosis that can be difficult to diagnose and treat. PG has a mixed nutritional deficiency and a history of ulcers. It is crucial to have a high degree of suspicion when making a diagnosis, as well as to look for associated diseases and start treatment as soon as possible.
Adult-onset Still’s disease as the first manifestation of acute myeloid leukemia: a case report
Authors: Ibrahim Ranim , Drie Tasneem , Shahada Zienab , Al Halabi Hayat , Kudsi Maysoun
Published: March 2023

Introduction and importance:

The association between adult-onset Still’s disease (AOSD) and malignancy has previously been observed. However, only a limited number of cases described a combination of AOSD and leukemia, none of which reported AOSD-related symptoms as the first manifestation of acute myeloid leukemia (AML). This presentation might represent a paraneoplastic syndrome or leukemic arthritis mimicking AOSD.

Case presentation:

Here the authors report a case of a 23-year-old female who fulfilled the Yamaguchi criteria for an AOSD diagnosis. She presented with complaints of polyarthritis, sore throat, and daily fever spikes with the appearance of a nonpruritic maculopapular salmon-colored rash. Her laboratory work showed marked pancytopenia, which led to a bone marrow examination and an AML diagnosis. The patient started receiving chemotherapy with considerable improvement in the AOSD-related symptoms.

Clinical discussion:

Patients with underlying malignancies could present with systemic features compatible with AOSD, which necessitates excluding malignancy in any patient with this presentation, specifically in light of some warning signs like pancytopenia.

Conclusion:

This case interprets a rare association between AOSD and AML. In addition, it highlights how crucial it is to be aware of the signs that should warn the clinician of a possible underlying malignancy in any patient presenting with AOSD-related symptoms.
Knowledge and attitude of organ donation in the Eastern region of Saudi Arabia and the influence of social media campaigns: a cross-sectional study
Authors: Alessa Mohammed Y. , Albedaiwi Maryam S. , Al Mousa Ali M. , Alhassan Ghadeer M. , Alnefaie Bayan T.
Published: March 2023

Background:

Previous studies showed organ donation to be less common in Arabic countries, and since there are not many studies exploring the perception toward organ donation, especially in the Eastern region of Saudi Arabia, this study aimed to assess the knowledge, attitude, and influence of social media campaigns on the willingness of organ donation.

Methods:

A cross-sectional study was conducted between September 2021 and April 2022 among social media users through an Arabic online survey exploring the population’s knowledge and attitude regarding organ donation and their willingness to donate. A total of 443 Saudi residents participated in the survey, with 376 of them meeting the required criteria.

Results:

In all, 85% of participants of the study’s calculated response rate were eligible to be included. One hundred ninety-eight of them (52.7%) were female, with age ranges between 18 and 29 years old (76.9%). The majority of the participants (63%) showed unwillingness to donate organs, with the highest rate among males (70.2%), aged above 30 (78.1%), and employees/students out of the healthcare sectors (69.5%). Inadequate knowledge was reported as the most common reason behind their rejection. Next to fears of operation and losing life, and the desire to donate to relatives only. Almost half of the participants (51.6%) agreed on the effect of social media on their behavior toward organ donation, with 187 of them (96.4%) referring to it as a positive effect which was significantly associated with the willingness to donate organs (P=0.006).

Conclusion:

The study results showed that most of the participants have neither proper knowledge nor willingness toward organ donation. Therefore, more strategies could be developed to increase the rate of donation in the Eastern region.
Preliminary results of laparoscopic cholecystectomy using real-time indocyanine green fluorescence: a cross-sectional study
Authors: Vu Van Quang , Le Van Thanh , Nguyen Hoang Ngoc Anh , Dang Kim Khue , Luong Mong Vu Anh
Published: March 2023

Objective:

Evaluating the results of laparoscopic cholecystectomy (LC) using indocyanine green (ICG) fluorescence.

Materials and methods:

This is a cross-sectional study of patients with LC using real-time fluorescent ICG to treat gallbladder disease from May 2021 to May 2022 in the 108 Military Central Hospital.

Results:

There were 68 patients who underwent LC using intraoperative ICG fluorescence for bile duct visualization. The mean age of the patients was 55.4±16.2, and the male/female ratio was 1.52. Chronic cholecystitis caused by stones accounted for the majority (51.47%). The authors detected 7.35% of cases with anatomical changes of the extrahepatic biliary tract using ICG fluorescence and clearly identified the anatomy of the common bile duct and the cystic duct at 100 and 92.65%, respectively. The average surgical time was 42.8±14.6 min. There were no postoperative complications or side effects from ICG; the average hospital stay was 2.8±1.5 days.

Conclusions:

ICG fluorescence cholangiography allows surgeons to easily identify critical anatomical landmarks in the LC. Thereby helping the surgery to be performed safely, avoiding severe complications due to damage to the biliary tract.
Efficacy of Propolis in the Prevention of Oral Mucositis in Patients Undergoing High-Dose Chemotherapy
Authors: Çakmak Seher , Nural Nesrin
Published: March 2023

Background

Oral mucositis is one of the most common symptoms in adults with a hematological cancer who are receiving high-dose chemotherapy. Propolis is a complementary and alternative method used to prevent oral mucositis in these patients.

Objective

The aim of this study was to determine the efficacy of propolis in the prevention of oral mucositis in patients receiving high-dose chemotherapy and/or hematopoietic stem cell transplantation.

Methods

A total of 64 patients, 32 in the propolis group and 32 in the control group, were enrolled in this prospective randomized controlled experimental study. Whereas the standard oral care treatment protocol was administered to the control group, aqueous propolis extract was applied to the propolis intervention group in addition to the standard oral care treatment protocol. Data collection forms included a Descriptive Information Form, the Karnofsky Performance Scale, the Cumulative Illness Rating Scale-Geriatric, Patient Follow-up Form, the World Health Organization Oral Toxicity Scale, and the National Cancer Institute Common Terminology Criteria for Adverse Events.

Results

The incidence and duration of oral mucositis were statistically significantly lower in the propolis intervention group than the control group, and the onset of oral mucositis and grade 2 to 3 oral mucositis occurred later (P < .05).

Conclusion

Propolis mouthwash combined with standard oral care treatment delayed the onset of oral mucositis and decreased its incidence and the number of days it lasted.

Implications for Practice

Mouthwash with propolis can be used as a nursing intervention to decrease oral mucositis and its symptoms in hematological cancer patients receiving high-dose chemotherapy.
Basal Cell Carcinoma in Xeroderma Pigmentosa: Reduced CD1a Expression as a Sensitive Predictor of Recurrence
Authors: El hanbuli Hala M , Abou Sari Mostafa A , Dawoud Noha M
Published: March 2023

Xeroderma pigmentosa (XP) is a rare genetic disorder that is characterized by defective DNA repair after ultraviolet induced damage with a great tendency for recurrent cutaneous malignancies including basal cell carcinoma (BCC). BCC is frequently linked to impaired local immune response with a major role played by Langerhans cells (LCs). The current study aims at investigating LCs in BCC specimens of XP and non-XP patients, in a trial to study its possible impact on tumor recurrence. It included 48 retrospective cases of primary facial BCC (18 for XP patients and 30 for non-XP controls). Each group was subdivided, based on the 5 years follow-up data, into recurrent and non-recurrent BCC groups. LCs were assessed immunohistochemically using the sensitive marker; CD1a. Results showed significantly reduced LCs count (intratumoral, peritumoral, and in perilesional epidermis) in XP patients compared with non-XP controls (P˂0.001 for all). Intratumoral (P=0.008), peritumoral (P=0.005), and perilesional epidermal (P=0.02) LCs mean values were significantly lower in recurrent versus non-recurrent BCC specimens. Also, within each group (XP and controls), LCs were of significantly lower means in recurrent versus non-recurrent cases (P≤0.001 for all). Regarding recurrent BCC cases, peritumoral LCs showed a significant positive correlation with 1ry BCC duration (P=0.05). Also, intratumoral and peritumoral LCs correlated positively with BCC relapse interval (P=0.04 for both). Among non-XP controls, periocular tumors had the least LCs count (22.00±3.56), whereas tumors located in the rest of the face had the greatest count (29.00±0.00) (P=0.02). Sensitivity and specificity of LCs to predict BCC recurrence in XP patients reached 100% in intartumoral area and perilesional epidermis when cutoff points were less than 9.5 and 20.5, respectively. In conclusion; reduced LC count in primary BCC specimens of XP patients and also in normal subjects could help to predict its recurrence. Thus, it might be identified as a risk factor for relapse to apply new strict therapeutic and preventive measures. This presents new avenue for the immunosurveillance against skin cancer relapse. However, being the first study to investigate that link in XP patients recommends further research to confirm.
Borderline With Bad Behavior: An Unusual Low-grade Serous Carcinoma With Dedifferentiation From a Serous Borderline Tumor
Authors: Strickland Amanda L. , Maniar Kruti P. , Tanner Edward , Shanes Elisheva , Jennings Lawrence , Wei Jian-Jun
Published: March 2023

The pathogenesis of serous ovarian tumors has been extensively investigated, with a dualistic model dividing these cancers into 2 groups. Type I tumors, including low-grade serous carcinoma, is characteristic for concurrent presence of borderline tumors, less atypical cytology, relatively indolent biologic behavior, and molecular aberrations related to the MAPK pathway with chromosomal stability. Meanwhile, type II tumors, such as high-grade serous carcinoma, are notable for no significant association with borderline tumors, higher grade cytology, more aggressive biologic behavior, and TP53 mutations along with chromosomal instability. We describe a case of morphologic low-grade serous carcinoma with focally increased cytologic atypia arising in serous borderline tumors involving both ovaries, which demonstrated highly aggressive behavior despite several years of surgical and chemotherapeutic management. Each recurrent specimen contained more uniform higher grade morphology than what was seen in the original specimen. Immunohistochemical and molecular studies in both the original tumor and the most recent recurrence demonstrate identical mutations in the MAPK genes, but with additional mutations in the latter, notably an acquisition of a variant of possible clinical significance in the SMARCA4 gene, which is associated with dedifferentiation and aggressive biologic behavior. This case challenges our current and still evolving understanding of the pathogenesis, biologic behavior, and expected clinical outcome of low-grade serous ovarian carcinomas. It also underscores the need for further investigation into this complicated tumor.
Rare Primary Fallopian Tube Grade 2 Neuroendocrine Tumor: A Case Report With Review of Literature
Authors: Kwon Grace J. , Jorgensen Jennifer R. , Vedere Tarunya R. , Sanders Melinda , Nam Gahie
Published: March 2023

Neuroendocrine neoplasms commonly arise from the gastrointestinal tract and lungs. Less commonly, they may occur in the gynecologic tract, typically within the ovary of a mature cystic teratoma. Primary neuroendocrine neoplasms of the fallopian tube are exceptionally rare and only a total of 11 cases have been reported in the literature. We describe the first case to our knowledge of a primary grade 2 neuroendocrine tumor of the fallopian tube in a 47-yr-old female. In this report, we describe the case’s unique presentation, review the published literature on primary neuroendocrine neoplasms of the fallopian tube, discuss the treatment options, and speculate on their origin and histogenesis.
THE EUROPEAN SHOCK SOCIETY MEETS THE IMMUNOSEP CONSORTIUM FOR PERSONALIZED SEPSIS TREATMENT
Authors: Giamarellos-Bourboulis Evangelos J. , Dimopoulos George , Flohé Stefanie , Kotsaki Antigoni , van der Poll Tom , Skirecki Tomasz , Torres Antoni , Netea Mihai G.
Published: March 2023

The unacceptable high mortality of severe infections and sepsis led over the years to understand the need for adjunctive immunotherapy to modulate the dysregulated host response of the host. However, not all patients should receive the same type of treatment. The immune function may largely differ from one patient to the other. The principles of precision medicine require that some biomarker is used to capture the immune function of the host and guide the best candidate therapy. This is the approach of the ImmunoSep randomized clinical trial (NCT04990232) where patients are allocated to treatment with anakinra or recombinant interferon gamma tailored to immune signs of macrophage activation-like syndrome and immunoparalysis respectively. ImmunoSep is a first-in-class paradigm of precision medicine for sepsis. Other approaches need to consider classification by sepsis endotypes, targeting T cell and application of stem cells. Basic principle for any trial to be successful is the delivery of appropriate antimicrobial therapy as standard-of-care taking into consideration not just the likelihood for resistant pathogens but also the pharmacokinetic/pharmacodynamic mode of action of the administered antimicrobial.
Opioid use disorder in cancer patients
Authors: Lewis Cara E.S. , Schutzer-Weissmann John , Farquhar-Smith Paul
Published: March 2023

Purpose of review

The misuse of opioids has increased significantly in recent decades. Historically, cancer patients have not been considered at risk of opioid misuse. However, cancer pain is common, and opioids are often prescribed. Guidelines addressing opioid misuse often exclude cancer patients. Given that misuse is associated with significant harm and a reduction in quality of life, it is important to understand the risk of opioid misuse in cancer patients and how we can recognise and treat it.

Recent findings

Early cancer diagnoses and treatments have improved cancer survival rates, leading to a larger population of cancer patients and survivors. Opioid use disorder (OUD) may precede a cancer diagnosis or may develop during or after treatment. The effect of OUD extends from an individual patient to a societal level. This review examines the increasing incidence of OUD in cancer patients, ways to identify patients with OUD such as behaviour change and screening scales, prevention of OUD such as limited and targeted opioid prescriptions, and evidence-based treatment suggestions for OUD.

OUD in cancer patients has only relatively recently been recognised as a growing problem. Early identification, involvement of the multidisciplinary team, and treatment can reduce the negative impact of OUD.
The Effect of Prophylactic Silicone Dressings on the Incidence of Pressure Injuries on Patients in the Acute Care Setting
Authors: Sugrue Claire , Avsar Pinar , Moore Zena , Patton Declan , O'Connor Tom , Nugent Linda , Budri Aglecia
Published: March 2023

PURPOSE:

To explore the effect of silicone dressings on the prevention of pressure injuries in patients cared for in the acute care setting. Three main comparisons were explored: silicone dressing versus no dressing, all anatomical areas; silicone dressing versus no dressing on the sacrum; and silicone dressing versus no dressing on the heels.

METHODS:

Using a systematic review methodology, published randomized controlled trials and cluster randomized controlled trials were included. The search was conducted from December 2020 to January 2021 using CINAHL, full text on EBSCOhost, MEDLINE on EBSCOhost, and Cochrane databases. The search returned 130 studies; 10 met inclusion criteria. Data were extracted using a predesigned extraction tool. The Cochrane Collaboration tool was used to assess the risk of bias and the certainty of the evidence was appraised using a software program specifically designed for this purpose.

RESULTS:

Silicone dressings probably reduce the incidence of pressure injuries compared to no dressings (relative risk [RR]: 0.40, 95% confidence interval [CI]: 0.31-0.53; moderate certainty evidence). Furthermore, silicone dressings probably reduce the incidence of pressure injuries on the sacrum compared to no dressings (RR: 0.44, 95% CI: 0.31-0.62; moderate certainty evidence). Finally, silicone dressings probably reduce the incidence of pressure injuries on the heels compared to no dressings (RR: 0.44, 95% CI: 0.31-0.62; moderate certainty evidence).

CONCLUSION:

There is moderate certainty evidence of the effect of silicone dressings as a component of a pressure injury prevention strategy. The main limiting factor in the study designs was a high risk of performance and detection bias. Although this is a challenge to achieve in trials such as these, consideration should be given to how the effect of this could be minimized. A further issue is the lack of head-to-head trials that limits clinicians' abilities to determine whether any of the products in this category are more effective than others.
Incidence and Characteristics of Suspected Deep Tissue Pressure Injuries on the Foot and Ankle
Authors: Canfor James , Michailidis Lucia , Williams Cylie
Published: March 2023

PURPOSE:

The purpose of this study was to measure the incidence of suspected deep tissue pressure injuries (DTPIs) in patients admitted to the hospital, describe their location, identify the related hospital length of stay, and explore any associations between intrinsic or extrinsic factors relevant to DTPI development.

DESIGN:

Retrospective review/audit of clinical data.

SUBJECTS AND SETTING:

We reviewed pertinent medical data from patients reported as developing a suspected deep tissue injury during hospital admission from January 2018 to March 2020. The study setting was a large tertiary public health service in Victoria, Australia.

METHODS:

Patients who developed a suspected deep tissue injury during hospital admission between January 2018 and March 2020 were identified through the hospital online risk recording system. Data were extracted from the relevant health records, including demographics, admission data, and pressure injury data. The incidence rate was expressed per 1000 patient admissions. Multiple regression analyses were used to determine associations between the time (days) to develop a suspected deep tissue injury and intrinsic (patient level) or extrinsic (hospital level) factors.

RESULTS:

Six hundred fifty-one pressure injuries were recorded during the audit period. A minority (9.5%; n = 62) of patients developed a suspected deep tissue injury; all were located on the foot and ankle. The incidence of suspected deep tissue injuries was 0.18 per 1000 patient admissions. The mean length of stay among patients who developed a DTPI was 59.0 (SD = 51.9) days as compared to a mean of 4.2 (SD = 11.8) days for all patients admitted to the hospital during this period. Multivariate regression analysis determined that the longer time (in days) to develop a pressure injury was associated with having a higher body weight (Coef = 0.02; 95% CI = 0.00 to 0.04; P = .043), not having off-loading (Coef =−3.63; 95% CI =−6.99 to −0.27; P = .034), and an increasing number of ward transfers (Coef = 0.46; 95% CI = 0.20 to 0.72; P = .001).

CONCLUSIONS:

Findings identified factors that may play a role in the development of suspected deep tissue injuries. A review of risk stratification in health services may be beneficial, with consideration to adjustments of procedural assessments of patients at risk.
Hematological malignancies as disorders negatively impacting specificities of the direct agglutination and rapid rK39 strip tests as reference diagnostics for visceral leishmanisis
Authors: Nail Abd Elsalam , Ahmed Ikram , Ali Osman Hussam , el Harith Abdallah
Published: March 2023

AbstractIntroduction: During several years of work in Sudan, we occasionally had been confronted with patients who presented clinical features highly suggestive of visceral leishmaniasis (VL) however direct agglutination test (DAT) readings that were either at the high negative or low positive titre range. Inquiries on the fate of those particular patients revealed mortality, undetermined diagnosis or that in some of them leukemia was finally diagnosed.Gap statement: Investigate as to what extent hematological malignancies (HMs) interfere with VL diagnosis.Aim: Evaluate specificity of DAT version newly developed in this study wherein sodium dodecyle sulphate (SDS) was incorporated as a test sample denaturant in comparison with a standard reference wherein β-mercaptoethanol (β-ME) was used in test execution.Methodology:  Seventy plasma samples from patients with HMs were collected and tested in a primary DAT version (P-DAT). The results obtained were compared with those of the rK39 strip test as VL reference diagnostic. HM samples revealing titres higher than the start dilution (1:100) in P-DAT were further tested in a β-ME- and urea- modified DAT versions. The specificity of the newly developed SDS-DAT was assessed against that of β-ME-DAT and rK39 strip tests as current reference diagnostics for VL.Results: Seven out of 70 patients with HMs scored positive outcomes (titre >1:3200) in P-DAT and 4 in the reference rK39 strip test. Of the 7 that tested positive in P-DAT or 4 in the reference rK39, none reacted at titre > 1:100 in the SDS-DAT.  Significant reduction in non-specific agglutination reactions was achieved as a result in respect to the HM plasma samples (P. value < 0.05).Conclusion: To establish desired specificity for VL diagnosis in respect to HMs and subsequently minimize or avoid serious side effects due to unjustified anti-leishmanials prescription the combined application of the SDS-DAT here described and an improved version of the rK39 for confirmation is recommended. Key words: Visceral leishmaniasis; diagnosis; hematological malignancies; DAT; rK39; anti-leishmanials; SDS.
From defaults to databases: parameter and database choice dramatically impact the performance of metagenomic taxonomic classification tools
Authors: Wright Robyn J. , Comeau André M. , Langille Morgan G. I.
Published: March 2023

In metagenomic analyses of microbiomes, one of the first steps is usually the taxonomic classification of reads by comparison to a database of previously taxonomically classified genomes. While different studies comparing metagenomic taxonomic classification methods have determined that different tools are ‘best’, there are two tools that have been used the most to-date: Kraken (k-mer-based classification against a user-constructed database) and MetaPhlAn (classification by alignment to clade-specific marker genes), the latest versions of which are Kraken2 and MetaPhlAn 3, respectively. We found large discrepancies in both the proportion of reads that were classified as well as the number of species that were identified when we used both Kraken2 and MetaPhlAn 3 to classify reads within metagenomes from human-associated or environmental datasets. We then investigated which of these tools would give classifications closest to the real composition of metagenomic samples using a range of simulated and mock samples and examined the combined impact of tool–parameter–database choice on the taxonomic classifications given. This revealed that there may not be a one-size-fits-all ‘best’ choice. While Kraken2 can achieve better overall performance, with higher precision, recall and F1 scores, as well as alpha- and beta-diversity measures closer to the known composition than MetaPhlAn 3, the computational resources required for this may be prohibitive for many researchers, and the default database and parameters should not be used. We therefore conclude that the best tool–parameter–database choice for a particular application depends on the scientific question of interest, which performance metric is most important for this question and the limit of available computational resources.
Video-rate Mid-infrared Photothermal Imaging by Single Pulse Photothermal Detection per Pixel
Authors: Yin Jiaze , Zhang Meng , Tan Yuying , Guo Zhongyue , He Hongjian , Lan Lu , Cheng Ji-Xin
Published: March 2023

By optically sensing the mid-infrared absorption induced photothermal effect, midinfrared photothermal (MIP) microscope enables super-resolution IR imaging and scrutinizing of biological systems in an aqueous environment. However, the speed of current lock-in based sample-scanning MIP system is limited to 1.0 millisecond or longer per pixel, which is insufficient for capturing dynamics inside living systems. Here, we report a single pulse laserscanning MIP microscope that dramatically increases the imaging speed by three orders of magnitude. We harness a lock-in free demodulation scheme which uses high-speed digitization to resolve single IR pulse induced contrast at nanosecond time scale. To realize single pulse photothermal detection at each pixel, we employ two sets of galvo mirrors for synchronized scanning of mid-infrared and probe beams to achieve an imaging line rate over 2 kHz. With video-rate imaging capability, we observed two types of distinct dynamics of lipids in living cells. Furthermore, by hyperspectral imaging, we chemically dissected a single cell wall at nanometer scale. Finally, with a uniform field of view over 200 by 200 μm2and 2 Hz frame rate, we mapped fat storage in free-movingC. elegansand live embryos.
Estimating the vertical ionization potential of single-stranded DNA molecules
Authors: Rooman Marianne , Pucci Fabrizio
Published: March 2023

The electronic properties of DNA molecules, defined by the sequence-dependent ionization potentials of nucleobases, enable long-range charge transport along the DNA stacks. This has been linked to a range of key physiological processes in the cells and to the triggering of nucleobase substitutions, some of which may cause diseases. To gain molecular-level understanding of the sequence dependence of these phenomena, we estimated the vertical ionization potential (vIP) of all possible nucleobase stacks in B-conformation, containing one to four Gua, Ade, Thy, Cyt or methylated Cyt. To do this, we used quantum chemistry calculations and more precisely the second-order Møller-Plesset perturbation theory (MP2) and three double-hybrid density functional theory (DFT) methods, combined with several basis sets for describing atomic orbitals. The calculated vIP of single nucleobases were compared to experimental data and those of nucleobase pairs, triplets and quadruplets, to observed mutability frequencies in the human genome, reported to be correlated with vIP values. This comparison selected MP2 with the 6-31G* basis set as the best of the tested calculation levels. These results were exploited to set up a recursive model, called vIPer, which estimates the vIP of all possible single-stranded DNA sequences of any length based on the calculated vIPs of overlapping quadruplets. vIPer’s vIP values correlate well with oxidation potentials measured by cyclic voltammetry and activities obtained through photoinduced DNA cleavage experiments, further validating our approach. vIPer is freely available on thegithub.com/3BioCompBio/vIPerrepository.
Mechanosensitive channel MscS is critical for termination of the bacterial hypoosmotic permeability response
Authors: Moller Elissa , Britt Madolyn , Schams Anthony , Cetuk Hannah , Anishkin Andriy , Sukharev Sergei
Published: March 2023

Free-living microorganisms are subjected to drastic changes in osmolarity. To avoid lysis under sudden osmotic down-shock, bacteria quickly expel small metabolites through the tension-activated channels MscL, MscS, and MscK. We examined five chromosomal knockout strains, ΔmscL, ΔmscS, a double knockout ΔmscSΔmscK, and a triple knockout ΔmscLΔmscSΔmscKin comparison to the wild-type parental strain. Stopped-flow experiments confirmed that both MscS and MscL mediate fast osmolyte release and curb cell swelling, but osmotic viability assays indicated that they are not equivalent. MscS alone was capable of rescuing the cell population, but in some strains MscL did not rescue and additionally became toxic in the absence of both MscS and MscK. Furthermore, MscS was upregulated in the ΔmscLstrain, suggesting either a cross-talk between the two genes/proteins or the influence of cell mechanics onmscSexpression. The data shows that for the proper termination of the permeability response, the high-threshold (MscL) and the low-threshold (MscS/MscK) channels must act sequentially. In the absence of low-threshold channels, at the end of the release phase, MscL should stabilize membrane tension at around 10 mN/m. Patch-clamp protocols emulating the tension changes during the release phase indicated that the non-inactivating MscL, residing at its own tension threshold, flickers and produces a protracted leakage. The MscS/MscK population, when present, stays open at this stage to reduce tension below the MscL threshold and silence the large channel. When MscS reaches its own threshold, it inactivates and thus ensures proper termination of the hypoosmotic permeability response. This functional interplay between the high- and low-threshold channels is further supported by the compromised osmotic survival of bacteria expressing non-inactivating MscS mutants.

Summary (for the table of contents)

The kinetics of hypotonic osmolyte release fromE. coliis analyzed in conjunction with bacterial survival. It is shown that MscL, the high-threshold ‘emergency release valve’, rescues bacteria from down-shocks only in the presence of MscS, MscK or other low-threshold channels that are necessary to pacify MscL at the end of the release phase.
A conserved local structural motif controls the kinetics of PTP1B catalysis
Authors: Yeh Christine Y. , Izaguirre Jesus A. , Greisman Jack B. , Willmore Lindsay , Maragakis Paul , Shaw David E.
Published: March 2023

Protein tyrosine phosphatase 1B (PTP1B) is a negative regulator of the insulin and leptin signaling pathways, making it a highly attractive target for the treatment of type II diabetes. For PTP1B to perform its enzymatic function, a loop referred to as the “WPD loop” must transition between open (catalytically incompetent) and closed (catalytically competent) conformations, which have both been resolved by X-ray crystallography. Although prior studies have established this transition as the rate-limiting step for catalysis, the transition mechanism for PTP1B and other PTPs has been unclear. Here we present an atomically detailed model of WPD-loop transitions in PTP1B based on unbiased, long-timescale molecular dynamics simulations and weighted ensemble simulations. We found that a specific WPD-loop region— the PDFG motif—acted as the key conformational switch, with structural changes to the motif being necessary and sufficient for transitions between long-lived open and closed states of the loop. Simulations starting from the closed state repeatedly visited open states of the loop that quickly closed again unless the infrequent conformational switching of the motif stabilized the open state. The functional role of the PDFG motif is supported by the fact that it (or the similar PDHG motif) is conserved across all PTPs. Bioinformatic analysis shows that the PDFG motif is also conserved, and adopts two distinct conformations, in deiminases, and the related DFG motif is known to function as a conformational switch in many kinases, suggesting that PDFG-like motifs may control transitions between structurally distinct, long-lived conformational states in multiple protein families.
Efficient and scalable prediction of spatio-temporal stochastic gene expression in cells and tissues using graph neural networks
Authors: Cao Zhixing , Chen Rui , Xu Libin , Zhou Xinyi , Fu Xiaoming , Zhong Weimin , Grima Ramon
Published: March 2023

The simulation of spatial stochastic models is highly computationally expensive, an issue that has severely limited our understanding of the spatial nature of gene expression. Here we devise a graph neural network based method to learn, from stochastic trajectories in a small region of space, an effective master equation for the time-dependent marginal probability distributions of mRNA and protein numbers at sub-cellular resolution for every cell in a tissue. Numerical solution of this equation leads to accurate results in a small fraction of the computation time of standard simulation methods. Moreover its predictions can be extrapolated to a spatial organisation (a cell network topology) and regions of parameter space unseen in its neural network training. The scalability and accuracy of the method suggest it is a promising approach for whole cell modelling and for detailed comparisons of stochastic models with spatial genomics data.
Farewell to single-well: An automated single-molecule FRET platform for high-content, multiwell plate screening of biomolecular conformations and dynamics
Authors: Hartmann Andreas , Sreenivasa Koushik , Schenkel Mathias , Chamachi Neharika , Schake Philipp , Krainer Georg , Schlierf Michael
Published: March 2023

Single-molecule FRET (smFRET) has become a widely used tool for probing the structure, dynamics, and functional mechanisms of biomolecular systems, and is extensively used to address questions ranging from biomolecular folding to drug discovery. Investigations by smFRET often require sampling of a large parameter space, for example, by varying one or more constituent molecular components in ten or more steps to reliably extract distances, kinetic rates, and other quantitative parameters. Confocal smFRET measurements, for example, which are amongst the widely used smFRET assays, are typically performed in a single-well format and measurements are conducted in a manual manner, making sampling of many experimental parameters laborious and time consuming. To address this challenge, we extend here the capabilities of confocal smFRET beyond single-well measurements by integrating a multiwell plate functionality into a confocal microscope to allow for continuous and automated smFRET measurements. We show that the multiwell plate assay is on par with conventional single-well smFRET measurements in terms of accuracy and precision yet enables probing tens to hundreds of conditions in a fully automized manner. We demonstrate the broad applicability of the multiwell plate assay towards DNA hairpin dynamics, protein folding, and competitive and cooperative protein–DNA interactions, revealing new insights that would be hard if not impossible to achieve with conventional single-well format measurements. The higher sampling density afforded by the multiwell plate format increases the accuracy of data analysis by at least 10-fold. We further showcase that the assay provides access to smFRET-based screening of drug–protein interactions. For the adaptation into existing instrumentations, we provide a detailed guide and open-source acquisition and analysis software. Taken together, the automated multiwell plate assay developed here opens up new possibilities to acquire high-content smFRET datasets for in-depth single-molecule analysis of biomolecular conformations, interactions, and dynamics.
Cerebellar Activity in Hemi-Parkinsonian Rats during Volitional Gait and Freezing
Authors: DeAngelo Valerie , Gehan Arianna , Paliwal Siya , Ho Katherine , Hilliard Justin D , Chiang Chia-Han , Viventi Jonathan , McConnell George C
Published: March 2023

Parkinson’s disease is a neurodegenerative disease characterized by gait dysfunction in the advanced stages of the disease. The unilateral 6-OHDA toxin-induced model is the most studied animal model of Parkinson’s disease, which reproduces gait dysfunction after greater than 68% dopamine (DA) loss in the substantia nigra pars compacta (SNc). The extent to which the neural activity in hemi-parkinsonian rats correlates to gait dysfunction and DAergic cell loss is not clear. In this paper we report the effects of unilateral DA depletion on cerebellar vermis activity using micro-electrocorticography (μECoG) during walking and freezing on a runway. Gait and neural activity were measured in 6-OHDA lesioned and sham lesioned rats at 14d, 21d, and 28d after infusion of 6-OHDA or control vehicle into the medial forebrain bundle (MFB) (n=20). Gait deficits in 6-OHDA rats were different from sham rats at 14d (p<0.05). Gait deficits in 6-OHDA rats improved at 21d and 28d except for run speed, which decreased at 28d (p=0.018). No differences in gait deficits were observed in sham lesioned rats at any time points. Hemiparkinsonian rats showed hyperactivity in the cerebellar vermis at 21d (p<0.05), but not at 14d and 28d, and the activity was reduced during freezing epochs in lobules VIa, VIb, and VIc (p<0.05). These results suggest that DAergic cell loss causes pathological cerebellar activity at 21d postlesion and suggests that compensatory mechanisms from the intact hemisphere contribute to normalized cerebellar activity at 28d. The decrease in cerebellar oscillatory activity during freezing may be indicative of neurological changes during freezing of gait in Parkinson’s disease patients making this region a potential location for biomarker detection. Although the unilateral 6-OHDA model presents gait deficits that parallel clinical presentations of Parkinson’s disease, further studies in animal models of bilateral DA loss are needed to understand the role of the cerebellar vermis in Parkinson’s disease.
The Role of HERG channel in the Secretion of Glucagon-Like Peptide-1 (GLP-1) from Murine Intestinal L-Cells
Authors: Liu Chang , Yuan Ying-Chao , Xie Rong-Rong , Wang Hao , Yang Jin-Kui
Published: March 2023

HERG ion channel is a member of the Voltage-gated potassium (Kv) channels. A reduction in HERG function reduces potassium efflux during repolarization. Previous research has shown that patients with long QT syndrome due to HERG mutations have increased secretion of the hormone glucagon-like peptide-1 (GLP-1). However, the role of HERG in GLP-1 secretion remains uncertain. Here we report that HERG is expressed in GLP-1-producing L-cells in rodent intestinal epithelium. In a mouse L-cell model (GLUTag cell line), downregulation of HERG significantly prolonged action potential duration, increased intracellular calcium concentration, and stimulated GLP-1 secretion after exposure to nutrients. These findings suggest that HERG in the intestine plays a direct role in GLP-1 secretion and may be a potential target for diabetes treatment.