bluuebunny/crossref_metadata_2025 huggingface dataset:
Kerion: an unusual presentation in the otolaryngology department
Authors: Ramachandran K , Arif M , Ugoji U , Davis B R
Published: March 2005

A 19-year-old farmer was referred by his general practitioner as an emergency to our otolaryngology department complaining of marked breathlessness of a few hours duration. He gave a three-day history of painful swelling and hair loss in the beard area of the right side of the neck. His upper airway was compromised unless extension of the neck was maintained. Larynx and pharynx were normal. The acute symptoms settled with intravenous antibiotics and hydrocortisone. Culture of skin scrapings revealed a growth of Tricophyton verrucosum. The neck swelling subsided after a course of oral griseofulvin followed by terbinafine. Difficulty in breathing due to fungal infection of the neck has not been previously reported in the English literature.
Natural health product–HIV drug interactions: a systematic review
Authors: Mills Edward , Montori Victor , Perri Dan , Phillips Elizabeth , Koren Gideon
Published: March 2005

The use of natural health products (NHPs) within the HIV community is high. Several NHPs have demonstrated interactions with HIV medications that could contribute to drug failure. We aimed to conduct a systematic review of clinical trials examining NHP–HIV drug interactions and their methodological characteristics. We searched electronic databases and unpublished resources independently, in duplicate. Nine studies were identified, eight clinical pharmacokinetics trials and one population-pharmacokinetics trial. Investigators studied four different herbal medicines (St John's wort, garlic, goldenseal and milk thistle) and one vitamin (vitamin C). Significant interactions were observed with St John's wort, garlic and vitamin C. However, methodological challenges exist to making the results directly generalizable to patients. This review finds that important drug level changes exist when NHPs are combined with HIV medications. Considering patient values and the implications of these studies, further research is urgently required to determine the extent of interactions with other commonly used NHPs.
Towards an evidence-based understanding of Peyronie's disease
Authors: Cavallini Giorgio
Published: March 2005

Aetiopathogenesis and therapy for Peyronie's disease are summarized below.

Aetiopathogenesis: (a) Plaque fibroblasts and their products provoke an immune response; (b) there are chromosomal differences between plaques and normal albuginea; (c) plaque fibroblasts are immortalized cells; (d) plaque fibroblasts demonstrate an impaired mitochondrial activity. These patterns provoke inflammation and they compel us to regard Peyronie's disease as being more similar to keloids than to scars.

Therapy: Medical therapy plays a pivotal role in the management of Peyronie's disease and should be performed prior to any surgery. Intraplaque collagenase, intraplaque verapamil, intraplaque interferon, oral acetyl-L-carnitine, oral propionyl-L-carnitine and oral colchicine have proved effective in Peyronie's disease. With the exception of collagenase, these drugs have displayed a number of activities whose final result is to improve immune response, to inhibit inflammation and to inhibit fibroblast metabolism and replication. Therefore, the primitive replicative (rather than reactive) nature of the disease is confirmed; this knowledge may be of help in the identification of new non-surgical therapies for Peyronie's disease.
Incidence and presentation of early syphilis diagnosed in HIV-positive gay men attending a central London outpatients' department
Authors: Ivens D , Patel M
Published: March 2005

We examined the incidence, presentation and sexual behaviour of gay men diagnosed with early syphilis at the Royal Free Hospital HIV department in 2002. A total of 1086 gay men attended and 31 were diagnosed with early syphilis (2.9/100 person years). Twenty-six (84%) of the men were symptomatic and 15 (48%) had documented negative serology within the previous six months. All of the men reported anal intercourse with a new partner in the previous three months. The results support offering regular serological screening to sexually active gay men attending our HIV outpatients' department.
Online diabetes education: design and evaluation with prospective diabetes camp counsellors
Authors: Heidgerken Amanda D , Lewin Adam B , Geffken Gary R , Gelfand Kenneth M , Storch Eric A , Malasanos Toree
Published: March 2005

An educational Website was designed by the Florida Initiative in Telehealth and Education group, and an online diabetes education test was developed using a sample of 60 children and young adults aged 8–22 years, all of whom had diabetes. The 31 items were analysed for item difficulty. Eight test items were eliminated as being unsuitable. The test was then used in 67 prospective diabetes counsellors (23 men, 44 women) who volunteered for a summer camp. Camp counsellors ranged in age from 17 to 33 years (mean 22 years, SD 3). The counsellors' mean pre-test scores were 80% and their mean post-test scores were 92%. There was a significant improvement ( P < 0.001) of approximately 1.25 questions from pre- to post-test. This supports the use of the online educational Website for training individuals working with children with diabetes. The Website may prove to be useful for online education in other areas of diabetes management.
Network basics for telemedicine
Authors: Gemmill Jill
Published: March 2005

Early telemedicine networks employed dedicated telecommunications circuits (e.g. leased digital lines) in which the sender and receiver were connected by a private circuit. More recently, the Internet has become widely available for general use, including telemedicine. The Internet was engineered to permit network paths to be shared by all users, so data transmission is fundamentally different from traditional, circuit-switched networks. Early telemedicine applications demonstrated the feasibility of Internet Protocol transmission. The basic performance criteria to use in evaluating newer digital communications technologies that carry both voice and data are: (1) bandwidth; (2) packet loss; (3) end-to-end delay; (4) jitter; (5) privacy and security. Network engineering involves performance trade-offs between the hardware, architecture, security and the budget available. A telemedicine application may be running over a network whose design is entirely under the user's control, or the application may employ some part of the Internet whose design is unknown to the user. If an application is not running to satisfaction, then a network engineer should be consulted.
Hazard of Noise Induced Hearing Loss (NIHL) among Operators of Music Recording/Retail Centres in Nigeria
Authors: Ologe Foluwasayo E. , Okoro Emmanuel O. , Akande Tanimola M.
Published: March 2005

We studied the level of music loudness to which operators of music recording/retail centre were exposed in order to determine their risk of work-related hearing loss. A survey of consenting operators of music recording centres on six main streets selected by simple random sampling at different locations of the town was carried out using a structured questionnaire. The sound level of the music from the music player speakers in each centre was measured using a sound level meter (Testo 815) duly calibrated with a sound level meter calibrator (Testo 0554.0009). Results were analyzed by simple descriptive statistics. The study involved 79 mainly male young adults aged 27.7 ± 6.8 years (SD). The measured sound levels in the centres ranged from 86-104dBA; with a mean of 96 ± 2.5dBA(SD). Exposure to this music loudness was for an average of 9 hours daily for an employment period averaging about 5 years. Thirty percent of the study population reduced music loudness by turning down the volume; 6.3% sat at six or more metres from the speakers; 10% used ear plugs occasionally and 7.6% had hearing assessment at some stage prior to the present study. The level of noise exposure of this population of young males is in excess of the threshold associated with irreversible hearing loss, and protection measures were less than optimal.
Shape Optimization with F-Function Balancing for Reducing the Sonic Boom Initial Shock Pressure Rise
Authors: Farhat Charbel , Argrow Brian , Nikbay Melike , Maute Kurt
Published: March 2005

A shape optimization methodology for reducing the initial shock pressure rise (ISPR) on the ground of a supersonic aircraft is presented. This methodology combines elements from the linearized aerodynamic theory such as Whitham's F-function with elements from the nonlinear aerodynamic theory such as the prediction of lift distribution by an Euler or a Navier-Stokes flow solver. It also features a concept of F-function lobe balancing that locates suitable positive and negative lobe pairs of the F-function, and modifies the shape of the aircraft to balance the areas of these lobes. The latter feature accelerates the convergence of the optimization procedure and forces it to generate an aircraft shape with a multi-shock ground signature, which reduces further the ISPR. This shaping technology is illustrated with an application to the Point of Departure aircraft developed by Lockheed-Martin for Phase I of DARPA's Quiet Supersonic Platform program. At M∞ = 1.5, a twenty-fold reduction of the ISPR on the ground, from 1.616 psf to 0.083 psf, is demonstrated while maintaining constant length, lift (weight), and inviscid drag. At M∞ = 2.0, a six-fold reduction of the ISPR on the ground, from 1.866 psf to 0.324 psf, is also demonstrated while maintaining constant length, lift (weight), and inviscid drag.
Periacetabular osteotomy in patients with Down’s syndrome
Authors: Katz D. A. , Kim Y.-J. , Millis M. B.
Published: March 2005

We treated eight dysplastic acetabula in six skeletally mature patients with Down’s syndrome by a modified Bernese periacetabular osteotomy. The mean age at the time of surgery was 16.5 years (12.8 to 28.5). Mean length of follow-up was five years (2 to 10.4).

Pre-operatively the mean (Tönnis) acetabular angle was 28°, the centre-edge angle was −9°, and the extrusion index was 60%; post-operatively they were 3°, 37°, and 17%, respectively. Two patients with post-operative (Tönnis) acetabular angles > 10° developed subluxation post-operatively and required secondary varus derotation femoral osteotomies. Another patient developed a late labral tear which was treated arthroscopically. All eight hips remain clinically stable, and are either asymptomatic or symptomatically improved.

These results suggest that the modified Bernese periacetabular osteotomy can be used successfully in the treatment of acetabular dysplasia in patients with Down’s syndrome.
Response of the tendon during limb lengthening
Authors: Szöke G. , Lee S.-H. , Simpson A. H. R. W. , Prescott J.
Published: March 2005

Little is known about the increase in length of tendons in postnatal life or of their response to limb lengthening procedures. A study was carried out in ten young and nine adult rabbits in which the tibia was lengthened by 20% at two rates 0.8 mm/day and 1.6 mm/day.

The tendon of the flexor digitorum longus (FDL) muscle showed a significant increase in length in response to lengthening of the tibia. The young rabbits exhibited a significantly higher increase in length in the FDL tendon compared with the adults. There was no difference in the amount of lengthening of the FDL tendon at the different rates. Of the increase in length which occurred, 77% was in the proximal half of the tendon.

This investigation demonstrated that tendons have the ability to lengthen during limb distraction. This occurred to a greater extent in the young who showed a higher proliferative response, suggesting that there may be less need for formal tendon lengthening in young children.
Monoblock and modular total shoulder arthroplasty for osteoarthritis
Authors: Mileti J. , Sperling J. W. , Cofield R. H. , Harrington J. R. , Hoskin T. L.
Published: March 2005

There are theoretical and practical advantages to modular rather than monoblock designs of prostheses for shoulder arthroplasty, but there are no reported studies which specifically compare the clinical and radiological results of their use. We have compared the results of unconstrained total shoulder arthroplasty for osteoarthritis using both types of implant. The monoblock design was used between 1992 and 1995 and the modular design after 1995. Both had cemented all-polyethylene glenoids, the monoblock with matched and the modular with mismatched radii of curvature. There were 34 consecutive shoulders in each group with a mean follow-up of 6.1 years in the first and 5.2 years in the second.

There were no significant differences in improvement of pain scores, active elevation, external rotation, internal rotation, patient satisfaction, or the Neer ratings between the two groups. Two of 28 glenoid components in the first group and six of 30 in the second met the criteria for being radiologically at risk for loosening (p = 0.25). There were no significant differences in clinical outcome or radiological changes between the first- and second-generation designs of implant for shoulder arthroplasty.
Thirty‐six month outcome data from a trial of counselling with chronically depressed patients in a general practice setting
Authors: Corney Roslyn , Simpson Sharon
Published: March 2005

Counsellors have been employed in general practice with little evidence of effectiveness in this setting. This randomized controlled trial examined long‐term effectiveness of short‐term counselling in general practice for patients with chronic depression, either alone or combined with anxiety. Participants were 181 patients recruited from nine general practitioners’ (GP) practices in Derbyshire by screening consecutive attenders using the Beck Depression Inventory. Both the experimental and control group received routine GP treatment but the experimental group were also referred to the practice counsellor. Depression and social adjustment were measured at baseline, 6, 12, and 36 months. There was an overall significant improvement in the actual scores over time, but there were no significant differences between the two groups on any of the measures at either 6, 12, or 36 months. Although fewer experimental group patients were still ‘cases’ on the BDI than controls at 6 and 12 months, this difference disappeared at 36 months. There was no evidence to demonstrate a long‐term effect of improved outcomes in those referred to counselling.
Ex‐clients' evaluation of bereavement counselling in a voluntary sector agency
Authors: Gallagher Mary , Tracey Anne , Millar Rob
Published: March 2005

This study aims to carry out an evaluation of bereavement counselling provided by a voluntary charity from the perspective of clients who had availed themselves of the service. A questionnaire survey of ex‐clients of one branch of a major voluntary sector bereavement care organization was carried out. Based on a sample of 89 returned questionnaires (representing a response rate of 45%), findings indicated that paraprofessional voluntary counsellors can provide a counselling service to bereaved people that satisfies the majority of clients who report positive experiences in counselling and post‐counselling outcomes, and generally rate their counselling as helpful. Nonetheless, there was a minority of ex‐clients who did not regard their status, 6 weeks after counselling, as being more positive. Further, the reputation of the voluntary agency within the community and among potential referrers and ex‐clients appears strong, offering additional positive evidence of the status of their bereavement counselling service in the locality.
The relationship between social deprivation and unilateral termination (attrition) from psychotherapy at various stages of the health care pathway
Authors: Self Roland , Oates Paula , Pinnock‐Hamilton Tia , Leach Chris
Published: March 2005

The relationship between social deprivation and attrition from psychotherapy was examined at various stages of the health care pathway. Data providing information on service users' discharge status gave a measure of attrition at different stages along this pathway. On the basis of their postcode, service users were allocated a Townsend deprivation score, which is a measure of social deprivation. Of the sample, 60% terminated therapy prior to agreed discharge at various pathway stages. Service users who failed to attend their first appointment had significantly higher social deprivation scores than those who completed therapy. Early terminators, who stopped attending before their fifth session, had a significantly higher level of social deprivation than the late terminators, and those who completed therapy. The late terminators did not significantly differ from completers on social deprivation. These results support earlier findings showing that socio‐economic status influences attrition from therapy. However, socio‐economic status only affects two stages of the pathway – attendance at the first appointment, and the early stage of attending therapy. It does not affect earlier or later stages of the pathway. Applying the health action process approach (HAPA) model to the results, the action/maintenance stage can be represented by attendance for therapy. Socio‐economic status influences this stage of the model, because social support and resources are important determinants for compliance. Earlier stages, characterized by HAPA as a decisional/motivation stage thought to be influenced by beliefs, was not affected by social deprivation. It is concluded that attrition from therapy should be studied separately for each pathway stage. Earlier conflicting findings on causes of attrition may have resulted from studying different combinations of pathway stages. Furthermore, high rates of attrition related to socio‐economic status raises serious questions about the external validity of therapy trials where these factors are not routinely reported, and the ecological validity of current service delivery models.
Identification of Ghrelin in Human Saliva: Production by the Salivary Glands and Potential Role in Proliferation of Oral Keratinocytes
Authors: Gröschl Michael , Topf Hans G , Bohlender Jörg , Zenk Johannes , Klussmann Sven , Dötsch Jörg , Rascher Wolfgang , Rauh Manfred
Published: March 2005

Background: We investigated whether ghrelin is present in human saliva, is produced by salivary glands, and physiologic consequences of these findings.

Methods: Expression of ghrelin and specific receptor mRNA was determined by PCR. Proteins were identified by immunoblotting and size-exclusion fast protein liquid chromatography (FPLC) with consecutive RIA. Specific RIAs were used for quantification of salivary total and bioactive ghrelin. Distribution of ghrelin was investigated by immunohistochemistry in cryosections of the salivary glands. The effect of ghrelin on incorporation of 5-bromo-2′-deoxyuridine as a measure of cell proliferation was investigated in primary oral keratinocytes.

Results:Ghrelin is produced by the salivary glands. The hormone was identified in saliva and glands by immunoblotting and by FPLC fractionation of saliva. Immunohistochemistry demonstrated ghrelin distribution in the salivary glands. The receptor was also produced by the glands and by oral keratinocytes and was shown to be functional. Comparison of total ghrelin values for healthy individuals (body mass index, 18–27 kg/m2) showed significantly lower concentrations in saliva than in serum (P <0.01). The correlation between both matrices was r2 = 0.56 (P <0.001) with a negative correlation to body mass index (r2 = 0.314; P <0.01). Bioactive acylated ghrelin was also present in saliva. Incubation of keratinocytes with ghrelin led to significantly increased cell proliferation (P <0.001). This effect could be completely suppressed by co-incubation with NOX-B11 (50 nmol/L), a novel specific inhibitor of acylated ghrelin.

Conclusions: Ghrelin in saliva is produced and released by salivary glands. The effect of ghrelin on oral cell proliferation adds to the pro-proliferative action of other salivary growth factors.
Chemoradiation after Surgery for High-Risk Head and Neck Cancer Patients: How Strong Is the Evidence?
Authors: Bernier Jacques , Cooper Jay S.
Published: March 2005

Learning Objectives

After completing this course, the reader will be able to: List the clinical and histopathologic risk factors that motivate a more aggressive adjuvant treatment in patients with locally advanced head and neck cancer.Evaluate the impact of post operative radiotherapy and chemoradiation on treatment outcome for a variety of efficacy and toxicity end points.Identify the most efficient chemotherapy agents in chemoradiation protocols for head and neck cancer patients.

Access and take the CME test online and receive 1 hour of AMA PRA category 1 credit at CME.TheOncologist.com

Patients with locally advanced, operable head and neck squamous cell carcinoma (HNSCC) are known to be at high risk of treatment failure, ranging from local regrowth to lymphatic spread to systemic dissemination. Attacking specifically each of these patterns of failure implies the use of a multimodal approach. Throughout the past two decades the management of stages III/IV HNSCC remained a matter of debate, especially with regards to treatment intensity and sequencing. Surgery and/or radiotherapy were the mainstay of local-regional treatment in patients with locally advanced disease, but treatment outcome often remained disappointing. In the hope of improving the prognosis after radical surgery, cisplatin-based combinations have been administered before surgery, in the interval between surgery and radiotherapy, or after radiotherapy. Until very recently these combinations, at best, decreased systemic failures without having a real impact on local outcome or survival. Indeed, until the mid-1990s, most trials that had tested postoperative combinations of chemotherapy and radiotherapy did not show any significant benefit. In 2004 level I evidence was established with the publication of the results of two large-scale, independent but similar trials conducted in Europe and the U.S. Both studies demonstrated that, compared with postoperative irradiation alone, adjuvant concurrent chemoradiation was more efficacious in terms of local-regional control and disease-free survival. With the publication of these two trials the evidence demonstrating the potential value of concurrent postoperative chemoradiotherapy in high-risk operable head and neck cancer is strong; however, additional studies and comparative analysis of the selection criteria and treatment outcomes across these two trials will be needed to gain a more accurate assessment of benefit and risk levels in specific patients with operable, locally advanced disease.
Eliminating Radioresistance With a Magnetic Ion‐Generator by Simultaneously Augmenting DNA Damage and Diminishing Immunosuppression
Authors: Zhang Ruru , Chen Mei , Zhou Hui , Liu Yan , Wang Yi , Chen Can , Li Yueping , Zeng Jianfeng , Cui Jiabin , Duan Ruixue , Gao Mingyuan
Published: February 2025

Radiotherapy (RT) hinges on DNA damage‐induced cancer cell death and the subsequent anti‐tumor immunity. However, the efficacy of RT is curtailed by cell cycle heterogeneity and an immunosuppressive tumor microenvironment, which foster radioresistance. Here an ion generator‐based RT enhancement strategy is demonstrated in a mouse model of the radioresistant tumor. The ion generator is degraded in the tumor microenvironment, resulting in iron‐triggered ferroptosis that enhanced immunogenic cell death and a manganese‐activated stimulator of interferon gene that reversed the immunosuppressive environment. As a result, the proposed strategy promotes dendritic cells maturity, augmentes CD8+ T cell infiltration of tumors, suppresses intratumoral myeloid‐derived suppressor cells, and limits the M2 macrophages polarization, indicating the formation of an immunoreactive microenvironment. Significantly, this approach impedes the growth of not just primary, but also distal metastatic tumors. It is thus believed that the current ion generator provides a robust and enduring countermeasure to radioresistant cancer and its metastasis, with potential implications for enhancing the efficacy of RT in clinically resistant tumors.
Monomolecule Coupled to Oxygen‐Doped Carbon for Efficient Electrocatalytic Hydrogen Peroxide Production
Authors: Liu Yanyan , Liu Shuling , Jiang Jianchun , Wei Xinao , Zhao Keke , Shen Ruofan , Wang Xiaopeng , Wei Min , Wang Yongfeng , Pang Huan , Li Baojun
Published: February 2025

The electrocatalytic production of hydrogen peroxide (H2O2) is an ideal alternative for the industrial anthraquinone process because of environmental friendliness and energy efficiency, depending on the activity and selectivity of catalysts. Carbon‐based materials possess prospects as candidate catalysts for the production of H2O2. Herein, cedar‐derived monolithic carbon catalysts modified with coupling oxygen doping and phthalocyanine molecules are synthesized. Cobalt phthalocyanine (CoPc) molecules are introduced onto the carbon surface to construct monomolecular active sites via π‐π stacking. The electronic structure of CoPc is modulated by oxygen doping on carbon substrates, mediated by monomolecular π‐π stacking. A synergistic effect optimally modulated the interaction between CoPc and key intermediate to H2O2. The energy barrier for oxygen reduction is reduced to optimize the selectivity to H2O2. CoPc@OCW provided up to 99% selectivity to H2O2 at 0.7 V versus RHE. In a three‐phase flow cell, CoPc@OCW achieved an H2O2 yield up to 10.4 mol·g−1·h−1 at 0.2 V versus RHE with stable running for 24 h. The advantages of carbon‐based catalysts including the adjustable chemical structure depending on π‐π stacking and electronic structure of carbon atoms through oxygen doping improved the catalytic performances in the production of H2O2. This proof‐to‐concept research demonstrates the potential application of carbon‐based molecular catalysts for electrochemical synthesis.
X‐Linked Gene Dosage and SOX2 Act as Key Roadblocks for Human Germ Cell Specification in Klinefelter Syndrome
Authors: He Wenteng , Luo Qing , Zhao Jian , Wang Mengting , Zhao Allan , Feng Luohua , Reda Ahmed , Lindgren Eva , Stukenborg Jan‐Bernd , Chen Jiayu , Deng Qiaolin
Published: February 2025

Klinefelter syndrome (KS), characterized by the presence of at least one extra X‐chromosome, is a common cause of male infertility. However, the mechanism underlying the failure of germline specification is not well studied. Intriguingly, the differentiation efficiency of female human pluripotent stem cells (hPSCs) is often lower than that of male. This study investigates how X‐linked gene dosage affects human primordial germ cell‐like cells (hPGCLCs) specification in both healthy and diseased conditions. This work reveals that X‐linked genes play a multifaceted role against the fate competency to hPGCLCs, with escape genes IGSF1 and CHRDL1 inhibiting the TGF‐beta/Activin A and BMP pathways, respectively. Notably, this work identifies a previously unrecognized role of SOX2, upregulated by the escape gene USP9X, elucidating a species‐specific function in the mammalian germline. The USP9X‐SOX2 regulatory axis profoundly influenced cellular metabolism, mitochondrial morphology, and progenitor competence in hPGCLCs specification. Furthermore, the inability to downregulate SOX2 and upregulate SOX17 in response to BMP signaling impedes downstream gene activation due to motif binding competition. These findings shed novel insights into the human germline specification by elucidating the divergent roles of SOX2 versus SOX17 in mammals, influenced by X‐linked gene dosage effects. These results offer potential applications for improving the induction efficiency of hPGCLCs, facilitating disease mechanistic studies.
Presentation and Longer‐Term Outcomes in Mosaic Trisomy 21 Causing Isolated Transient Abnormal Myelopoiesis
Authors: Mehra Anna‐Thérèse , Wojcik Monica H.
Published: February 2025

Transient abnormal myelopoiesis (TAM) is a transitory, myeloproliferative condition nearly exclusively present in infants with complete trisomy 21 (T21), or in its rare form, T21 mosaicism. We present here a case study of a neonate diagnosed with T21 mosaicism and TAM who did not exhibit the typical phenotypic features of down syndrome (DS), but displayed hematologic abnormalities, in addition to hepatosplenomegaly. Initial genetic testing suggested acute myeloid leukemia (AML) but subsequent evaluations were indicative of T21 mosaicism confined to the myeloid cell line, with negative results from lymphocytes cultured from a skin biopsy. A pathogenic GATA1 variant was found in the bone marrow in addition to three copies of RUNX1, associated with aberrant hematopoiesis in TAM. The infant responded to a brief course of chemotherapy and demonstrated normal growth and development at four years of age. In addition to this case, we identified 25 cases from the literature of mosaic T21 restricted to the myeloid cell line supporting normal development following treatment for TAM. As this case and the literature review demonstrate, T21 mosaicism apparently isolated to the bone marrow is unlikely to be associated with systemic or neurodevelopmental manifestations of DS.
Plasma Alzheimer's disease biomarker relationships with incident abnormal amyloid PET
Authors: Cogswell Petrice M. , Wiste Heather J. , Weigand Stephen D. , Therneau Terry M. , Griswold Michael E. , Braunstein Joel B. , West Tim , Verghese Philip B. , Graff‐Radford Jonathan , Algeciras‐Schimnich Alicia , Lowe Val J. , Schwarz Christopher G. , Senjem Matthew L. , Gunter Jeffrey L. , Knopman David S. , Vemuri Prashanthi , Petersen Ronald C. , Jack Clifford R.
Published: February 2025

INTRODUCTION

Limited data exist on the utility of plasma biomarkers to predict incident abnormal amyloid positron emission tomography (PET). In this study we evaluate the association of plasma Alzheimer's disease (AD) biomarkers with amyloid PET progression among initially amyloid PET negative (A−) individuals.

METHODS

We included 290 A−, cognitively unimpaired Mayo Clinic Study of Aging participants. We estimated the association of each baseline plasma biomarker with progression from A− to A+ and with rate of amyloid PET change.

RESULTS

Interquartile range differences in amyloid beta 42/40, percent phosphorylated tau 217 (%p‐tau217), and Amyloid Probability Score 2 were associated with 1.29 (P = 0.09), 1.38 (P < 0.001), and 1.20 (P = 0.05) increases, respectively, in the hazard of progression from A− to A+ and 0.27 (P = 0.16), 0.50 (P = 0.007), and 0.28 (P = 0.15) Centiloid/year increases, respectively, in annual rate of amyloid PET change.

DISCUSSION

Plasma %p‐tau217 may be a useful screening tool to enrich for participants with increased likelihood of progressing from normal to abnormal amyloid PET in a primary prevention trial.

Highlights

Plasma phosphorylated tau 217 was associated with amyloid positron emission tomography progression, negative to positive.

The associations were weaker for amyloid beta 42/40 and Amyloid Probability Score 2.

Age and apolipoprotein E ε4 carriership were also important predictors.

These markers may be useful for enrichment of a primary prevention trial.
Prescription opioid use and cognitive function in older adults with chronic pain: A population‐based longitudinal cohort study
Authors: Wei Yu‐Jung Jenny , Winterstein Almut G. , Schmidt Siegfried , Fillingim Roger B. , Schmidt Stephan , Daniels Michael J. , DeKosky Steven T.
Published: February 2025

INTRODUCTION

Whether prescription opioid exposure, duration, and dose are associated with cognitive function remains inconclusive.

METHODS

A longitudinal cohort among 3097 older adults with chronic pain and without dementia was conducted using Health and Retirement Study (HRS) linked to Medicare data from 2006 to 2020. Prescription opioid exposure, cumulative use for ≥ 90 days, and high‐dose use (≥ 90 morphine milligram equivalents [MME] daily) were assessed biennially. Memory score and dementia probability were derived from HRS cognitive measures and analyzed using linear mixed‐effects models.

RESULTS

Adjusted memory decline and dementia probability were not statistically different between patients with (vs. without) opioid exposure and between patients with cumulative use for ≥ 90 days (vs. < 90 days) but were higher between participants with high‐dose opioid use (vs. low‐dose) at the end of the follow‐up.

DISCUSSION

Prescription opioid exposure and duration were not associated, but high‐dose opioid use was associated with greater memory decline and dementia probability.

Highlights

Opioid use versus no use was not related to memory decline and dementia probability.

Long‐term opioid use was not related to memory decline and dementia probability.

High‐dose opioid use was related to greater memory decline and dementia probability.
The protective effects of melatonin against electromagnetic waves of cell phones in animal models: A systematic review
Authors: Amiri Mohammad , Khazaie Habibolah , Mohammadi Masoud
Published: February 2025

Background

Due to the widespread use of cell phone devices today, numerous research studies have focused on the adverse effects of electromagnetic radiation on human neuropsychological and reproductive systems. In most studies, oxidative stress has been identified as the primary pathophysiological mechanism underlying the harmful effects of electromagnetic waves. This paper aims to provide a holistic review of the protective effects of melatonin against cell phone‐induced electromagnetic waves on various organs.

Methods

This study is a systematic review of articles chosen by searching Google Scholar, PubMed, Embase, Scopus, Web of Science, and Science Direct using the keywords ‘melatonin’, ‘cell phone radiation’, and ‘animal model’. The search focused on articles written in English, which were reviewed and evaluated. The PRISMA process was used to review the articles chosen for the study, and the JBI checklist was used to check the quality of the reviewed articles.

Results

In the final review of 11 valid quality‐checked articles, the effects of melatonin in the intervention group, the effects of electromagnetic waves in the case group, and the amount of melatonin in the chosen organ, i.e. brain, skin, eyes, testis and the kidney were thoroughly examined. The review showed that electromagnetic waves increase cellular anti‐oxidative activity in different tissues such as the brain, the skin, the eyes, the testis, and the kidneys. Melatonin can considerably augment the anti‐oxidative system of cells and protect tissues; these measurements were significantly increased in control groups. Electromagnetic waves can induce tissue atrophy and cell death in various organs including the brain and the skin and this effect was highly decreased by melatonin.

Conclusion

Our review confirms that melatonin effectively protects the organs of animal models against electromagnetic waves. In light of this conclusion and the current world‐wide use of melatonin, future studies should advance to the stages of human clinical trials. We also recommend that more research in the field of melatonin physiology is conducted in order to protect exposed cells from dying and that melatonin should be considered as a pharmaceutical option for treating the complications resulting from electromagnetic waves in humans.
One 3D Zn‐MOF for Fluorescence Sensing and Visualization Detection of Biomarker and Antibiotic
Authors: Liu Tingting , Ji Mengna , Hao Hongguo , Dou Jianmin , Yan Hui , Jiang Jingjing , Li Yunwu , Wang Suna
Published: February 2025

One 3D Zn‐MOF, namely, {[Zn2(L)(OH)(DMF)]}n was selected based on the flexible ether oxygen carboxylic acid 3‐(3,5‐dicarboxylatobenzyloxy)benzoic acid (H3L). Zn‐MOF was able to specifically recognize the biomarker methylmalonic acid (MMA) and antibiotic tetracycline (TC) through fluorescence enhancement and ratio mechanism, with the detection limits (LOD) as low as 1.29 and 0.26 μM, respectively. It also has high selectivity and rapid response characteristics. In particular, the visual detection was significantly enhanced in the presence of Tb3+ through antenna effect. To explore the potential application, fluorescent test strips and mixed matrix membrane (MMM) were successfully prepared to realize visual detection. The recovery rates of MMA and TC in simulated urine and actual water systems were 95.3%–100.5% and 93.5%–94.7%, respectively, indicating that Zn‐MOF provided the possibility for detecting biomarker and antibiotic in practical systems.
Plasma proteomic profiles predict individual future osteoarthritis risk
Authors: Kang Zijian , Zhang Jianzheng , Liu Wenxin , Zhu Chen , Zhu Ying , Li Ping , Li Kai , Tong Qiang , Dai Sheng‐Ming
Published: February 2025

Objective

Osteoarthritis (OA) is a widespread degenerative joint disease that causes a considerable socioeconomic burden. Despite progress in genetic and environmental insights, early diagnosis is still limited by the lack of evident symptoms during the initial phases and accurate biomarkers. This study aims to identify plasma proteins associated with future risk of OA and develop a predictive model.

Methods

We conducted a large‐scale proteomic analysis of 45,307 participants from the UK Biobank, excluding those with baseline OA. Plasma samples were assayed using the Olink Explore Proximity Extension Assay targeting 1,463 unique proteins. Clinical variables and OA outcomes were extracted and linked to electronic health records. A predictive model was constructed using the LightGBM machine learning method, and the SHapley Additive exPlanations (SHAP) were applied to evaluate the importance of variables.

Results

We identified a panel of proteins significantly associated with the risk of developing OA. Notably, after adjusting for multiple confounders, Collagen Type IX Alpha 1 Chain (COL9A1) and Cartilage Acidic Protein 1 (CRTAC1) were the most significant predictors of incident OA, with hazard ratios (HR) of 1.54 (95% confidence interval [CI]:1.48‐1.61) and 1.65 (95% CI:1.54‐1.78), respectively. SHAP analysis allowed a profound interpretation of the contribution of each protein and clinical variable to the model, revealing the multifactorial nature of OA risk prediction. The temporal trajectories of plasma proteins indicated that the levels of COL9A1 and CRTAC1 began to deviate from normal for more than a decade before OA onset, suggesting their potential use in early detection strategies. The predictive model, developed using the LightGBM algorithm, integrated proteins with clinical covariates and demonstrated an area under the curve (AUC) of 0.729 for 5‐year OA prediction, 0.721 for 10‐year prediction, and 0.723 for all incident OA. The predictive accuracy of the model was further enhanced for hip and knee OA, achieving AUCs of 0.820 and 0.803 for 5‐year predictions.

Conclusion

Our study identified the role of plasma proteomics in predicting future OA risk, which could contribute to preemptive measures. The innovative model, which integrates proteomic biomarkers with clinical data, offers a potential tool for risk assessment, potentially optimizing OA management strategies and enhancing prevention efforts.
A Chemiluminescent Hydrogen Sulfide Probe with Multimodal Validation for Inflammation Diagnosis In Vivo
Authors: Wei Lianzhu , Chen Ling , Li Yuanyong , Yang Maocheng , Yang Mingyan , Geng Wen-Chao , Yuan Zeli , Gao Jie
Published: February 2025

Probes capable of simultaneously detecting and differentiating biothiols is crucial yet challenging in optical chemical sensing. In this study, we design a multimodal probe, CL‐NBD, through integrating chemiluminescence (high sensitivity and signal‐to‐noise ratio), absorption (visual discrimination by the naked eye), and fluorescence to distinguish various biothiol species. CL‐NBD exhibits distinct signal response modes for hydrogen sulfide (H2S), cysteine/homocysteine (Cys/Hcy), and glutathione. Upon activation by biothiols, CL‐NBD produces chemiluminescence and enhances fluorescence at 515 nm, allowing for selective biothiol detection over other reactive species. Additionally, the probe reveals specific absorbance enhancement at 531 nm for H2S, facilitating its selective detection. For Cys/Hcy, the probe enhances absorbance at 475 nm and fluorescence at 550 nm, enabling distinctive detection capabilities. Remarkably, CL‐NBD was applied to visualize biothiol levels both at the cellular level and in vivo.
Methionine Restriction Exerts Anti‐Tumor Immunity via Joint Intervention of T‐Bet Palmitoylation in Gastric Cancer
Authors: Xin Lin , Xu He‐Song , Fan Luo‐Jun , Liu Chuan , Zou Yong‐Hui , Zhou Qi , Yue Zhen‐Qi , Gan Jin‐Heng , Liu Jiang
Published: February 2025

Background

Methionine restriction (MR) exerts an anti‐tumor immunomodulatory role. Th1 cells facilitate CD8+ cytotoxic T cell activation and targeted tumor cell killing. Our previous work shows that MR enhances the immunotherapy effect of PD‐L1/PD‐1 blockade on gastric cancer, MR can simultaneously inhibit Th1 cell differentiation, which may affect their synergistic therapeutic outcome. We aim to elucidate the molecular mechanism of MR regulating Th1 cell activation in gastric cancer.

Methods

Murine Foregastric Carcinoma (MFC) cells were injected into 615 mice to establish transplanted tumor models, which were then treated with an MR diet or combined with 2‐bromopalmitate (2‐BP). CD4+T cells were cultured with deficient methionine. The acyl‐biotinyl exchange (ABE) method was to detect T‐bet palmitoylation and cycloheximide experiments to detect protein stability. GPS‐Palm tool was employed to screen palmitoyltransferases. The impact of T‐bet palmitoylation on the pro‐tumor‐killing effect of Th1 cells was examined.

Results

MR enhanced anti‐PD‐1's inhibition of tumor growth, while concurrently suppressing the increased Th1 cells. Combined with 2‐BP further inhibited tumor and increased Th1 cells. Suppressing Th1 activity attenuated 2‐BP's synergistic therapeutic effect and reduced CD8+ GZMB+ T cells. MR inhibited Th1 differentiation by reducing T‐bet expression, 2‐BP treatment restored, while T‐bet interference reversed 2‐BP's effect. MR increased palmitoylation and T‐bet underwent palmitoylation modification. ZDHHC23 mediated T‐bet palmitoylation and promoted T‐bet degradation. MR promoted T‐bet degradation, thereby decreasing T‐bet content, inhibiting Th1 cell polarization and CD8+ T cell killing effect.

Conclusions

MR combined with T‐bet palmitoylation intervention promotes Th1 polarization and CD8+ T cell toxicity, thereby enhancing anti‐tumor immunity in gastric cancer.
Use of Whole Cells and Cell‐Free Extracts of Catalase‐Deficient E. coli for Peroxygenase‐Catalyzed Reactions
Authors: Ebrecht Ana C. , Luelf U. Joost , Govender Kamini , Opperman Diederik J. , Urlacher Vlada B. , Smit Martha S.
Published: February 2025

Unspecific peroxygenases (UPOs) and cytochrome P450 monooxygenases (CYPs) with peroxygenase activity are becoming the preferred biocatalysts for oxyfunctionalization reactions. While whole cells (WCs) or cell‐free extracts (CFEs) of Escherichia coli are often preferred for cofactor‐dependent monooxygenase reactions, hydrogen peroxide (H2O2) driven peroxygenase reactions are generally performed with purified enzymes, because the catalases produced by E. coli are expected to quickly degrade H2O2. We used the CRISPR/Cas system to delete the catalase encoding chromosomal genes, katG, and katE, from E. coli BL21‐Gold(DE3) to obtain a catalase‐deficient strain. A short UPO, DcaUPO, and two CYP peroxygenases, SscaCYP_E284A and CYP102A1_21B3, were used to compare the strains for peroxygenase expression and subsequent sulfoxidation, epoxidation, and benzylic hydroxylation activity. While 10 mM H2O2 was depleted within 10 min after addition to WCs and CFEs of the wild‐type strain, at least 60% remained after 24 h in WCs and CFEs of the catalase‐deficient strain. CYP peroxygenase reactions, with generally lower turnover frequencies, benefited the most from the use of the catalase‐deficient strain. Comparison of purified peroxygenases in buffer versus CFEs of the catalase‐deficient strain revealed that the peroxygenases in CFEs generally performed as well as the purified proteins. We also used WCs from catalase‐deficient E. coli to screen three CYP peroxygenases, wild‐type SscaCYP, SscaCYP_E284A, and SscaCYP_E284I for activity against 10 substrates comparing H2O2 consumption with substrate consumption and product formation. Finally, the enzyme‐substrate pair with highest activity, SscaCYP_E284I, and trans‐β‐methylstyrene, were used in a preparative scale reaction with catalase‐deficient WCs. Use of WCs or CFEs from catalase‐deficient E. coli instead of purified enzymes can greatly benefit the high‐throughput screening of enzyme or substrate libraries for peroxygenase activity, while they can also be used for preparative scale reactions.
Accounting for Renewable Energy: Investigating Emerging Topics and Research Pathways
Authors: De Villiers Charl , Principale Salvatore , Galeotti Rubina Michela , Cicchini Daniela
Published: February 2025

This paper presents a structured and systematic literature review (SLR) and critique of the literature on the opportunities and challenges of accounting, auditing, and renewable energy sources to identify trends and research streams and construct an agenda for future research. We collected a corpus of 229 academic articles searching in the 89 Chartered Association of Business School (CABS) accounting journals ranked 1, 2, 3, 4, and 4* over a period of 22 years. A total of 32 academic articles were included in the core analysis showing a total number of 2418 citations. We identify three research streams, namely 1) sustainability accounting and accounting for renewable energy; 2) the relationship between accounting, institutions, and the environment; and 3) environmental accounting, management, and sustainable development. The main theoretical and practical implications of this paper's findings are that the role of accounting and auditing for renewable energy is a prominent research topic for academics, practitioners, decision‐makers, and policy‐makers to consider.
Doxorubicin Plus Dacarbazine Versus Doxorubicin Plus Ifosfamide in Combination With Regional Hyperthermia in Patients With Advanced Leiomyosarcoma: A Propensity Score‐Matched Analysis
Authors: Berclaz Luc M. , Jurinovic Vindi , Burkhard‐Meier Anton , Abdel‐Rahman Sultan , Albertsmeier Markus , Klein Alexander , Dürr Hans Roland , Schmidt‐Hegemann Nina‐Sophie , Knösel Thomas , Kunz Wolfgang G. , Stutz Emanuel , von Bergwelt‐Baildon Michael , Di Gioia Dorit , Lindner Lars H.
Published: February 2025

Background

Dacarbazine is currently considered the better combination partner for doxorubicin compared to ifosfamide for the treatment of leiomyosarcoma (LMS). Regional hyperthermia (RHT) combined with neoadjuvant chemotherapy has been shown to improve survival in patients with locally advanced high‐risk STS. We sought to evaluate the role of doxorubicin and dacarbazine (AD) versus doxorubicin and ifosfamide (AI) in combination with RHT in patients with LMS.

Methods

Patients with locally advanced high‐grade LMS, including limited metastases, eligible for RHT and first‐line treatment with either AI + RHT or AD + RHT between 2014 and 2022 were retrospectively evaluated. Endpoints were progression‐free survival (PFS) and overall survival (OS). Patients were matched using propensity scores, which were estimated with a logistic regression model accounting for tumor site, presence of metastasis, surgery, and radiotherapy.

Results

A total of 105 patients were included in this study, of which 101 were included in the propensity score‐matched cohort. In the matched cohort, treatment with AD + RHT was associated with a significantly improved PFS (HR 0.32, 95% CI 0.13–0.74, p = 0.0081). Multivariable analysis revealed several significant predictors of PFS, including treatment with AD + RHT (HR 0.42, 95% CI 0.19–0.92, p = 0.031).

Conclusion

Treatment with AD + RHT showed improved PFS and better treatment tolerability compared to AI + RHT. Our results support the use of AD instead of AI for the treatment of patients with LMS in combination with RHT.