bluuebunny/crossref_metadata_2025 huggingface dataset:
High Arctic seawater and coastal soil microbiome co-occurrence and composition structure and their potential hydrocarbon biodegradation
Authors: Freyria Nastasia J , Góngora Esteban , Greer Charles W , Whyte Lyle G
Published: July 2024

The accelerated decline in Arctic sea-ice cover and duration is enabling the opening of Arctic marine passages and improving access to natural resources. The increasing accessibility to navigation and resource exploration and production brings risks of accidental hydrocarbon releases into Arctic waters, posing a major threat to Arctic marine ecosystems where oil may persist for many years, especially in beach sediment. The composition and response of the microbial community to oil contamination on Arctic beaches remain poorly understood. To address this, we analyzed microbial community structure and identified hydrocarbon degradation genes among the Northwest Passage intertidal beach sediments and shoreline seawater from five high Arctic beaches. Our results from 16S/18S rRNA genes, long-read metagenomes, and metagenome-assembled genomes reveal the composition and metabolic capabilities of the hydrocarbon microbial degrader community, as well as tight cross-habitat and cross-kingdom interactions dominated by lineages that are common and often dominant in the polar coastal habitat, but distinct from petroleum hydrocarbon-contaminated sites. In the polar beach sediment habitats, Granulosicoccus sp. and Cyclocasticus sp. were major potential hydrocarbon-degraders, and our metagenomes revealed a small proportion of microalgae and algal viruses possessing key hydrocarbon biodegradative genes. This research demonstrates that Arctic beach sediment and marine microbial communities possess the ability for hydrocarbon natural attenuation. The findings provide new insights into the viral and microalgal communities possessing hydrocarbon degradation genes and might represent an important contribution to the removal of hydrocarbons under harsh environmental conditions in a pristine, cold, and oil-free environment that is threatened by oil spills.
International Conflict, Border Security, and State Capacity: Case of British India
Authors: Park Jeongmin
Published: July 2024

The dominant approach to war and state-building attributes state development to wartime growth of extractive capacity. Yet we know little about the administrative foundation through which extractive capacity is increased spatially, beyond the central policy level. Using railways as an example of a state-building asset, I revisit the role of external threat on state-building, with evidence drawing upon detailed historical data from nineteenth-century India during a crucial period of Anglo–Russo rivalry. I find that conflict with Russia led to expansion of railways in the Northwest Frontier bordering Afghanistan, the buffer between British India and Russia, which led to improved performance of local tax administrators. The findings suggest that external conflict promotes state development through provision of logistical networks enabling greater administrative efficiency in geographically distant frontiers.
Management of Clostridioides difficile infection: an Italian Delphi consensus
Authors: Bassetti Matteo , Cascio Antonio , De Rosa Francesco Giuseppe , Meschiari Marianna , Parrella Roberto , Petrosillo Nicola , Armuzzi Alessandro , Caprioli Flavio , Dentali Francesco , Pani Marcello , Pilotto Alberto , Restelli Umberto , Sanguinetti Maurizio
Published: July 2024

Background

Clostridioides difficile infection (CDI), a leading cause of nosocomial deaths, is a microbiota-mediated disease. As such, the use of broader spectrum antibiotics, such as vancomycin and metronidazole, can prime the gastrointestinal tract to become more prone to CDI recurrences. Fidaxomicin, a narrow-spectrum antibiotic, has been demonstrated to be superior in preventing recurrence and in preserving the intestinal microbiota; however, widespread employment worldwide has been hindered due to high acquisition costs.

Objectives

To integrate the currently available guidelines on the management of CDI and to shed light on the timeliest employment of fidaxomicin.

Methods

An expert panel was gathered to obtain consensus using Delphi methodology on a series of statements regarding the management of CDI and on appropriate antibiotic use.

Results

Consensus was reached on 21 of the 25 statements addressing the management of CDI.

Conclusions

Delphi methodology was used to achieve consensus on the management of CDI, on the identification of patients at risk of recurrences or severe infection, and on the most appropriate use of fidaxomicin, with the final aim of fostering clinical practice application of treatment algorithms proposed by previous guidelines, in absolute synergy. It could be an important tool to promote more appropriate and cost-effective CDI treatments in European settings with limited resources, like Italy.
In silico gepotidacin target mining among 33 213 global Neisseria gonorrhoeae genomes from 1928 to 2023 combined with gepotidacin MIC testing of 22 gonococcal isolates with different GyrA and ParC substitutions
Authors: David Alexandra , Golparian Daniel , Jacobsson Susanne , Stratton Caleb , Lan Pham Thi , Shimuta Ken , Sonnenberg Pam , Field Nigel , Ohnishi Makoto , Davies Christopher , Unemo Magnus
Published: July 2024

Objectives

The novel dual-target triazaacenaphthylene, gepotidacin, recently showed promising results in its Phase III randomized controlled trial for the treatment of gonorrhoea. We investigated alterations in the gepotidacin GyrA and ParC targets in gonococci by in silico mining of publicly available global genomes (n = 33 213) and determined gepotidacin MICs in isolates with GyrA A92 alterations combined with other GyrA and/or ParC alterations.

Methods

We examined gonococcal gyrA and parC alleles available at the European Nucleotide Archive. MICs were determined using the agar dilution method (gepotidacin) or Etest (four antimicrobials). Models of DNA gyrase and topoisomerase IV were obtained from AlphaFold and used to model gepotidacin in the binding site.

Results

GyrA A92 alterations were identified in 0.24% of genomes: GyrA A92P/S/V + S91F + D95Y/A/N (0.208%), A92P + S91F (0.024%) and A92P (0.003%), but no A92T (previously associated with gepotidacin resistance) was found. ParC D86 alterations were found in 10.6% of genomes: ParC D86N/G (10.5%), D86N + S87I (0.051%), D86N + S88P (0.012%) and D86G + E91G (0.003%). One isolate had GyrA A92P + ParC D86N alterations, but remained susceptible to gepotidacin (MIC = 0.125 mg/L). No GyrA plus ParC alterations resulted in a gepotidacin MIC > 4 mg/L. Modelling of gepotidacin binding to GyrA A92/A92T/A92P suggested that gepotidacin resistance due to GyrA A92T might be linked to the formation of a new polar contact with DNA.

Conclusions

In silico mining of 33 213 global gonococcal genomes (isolates from 1928 to 2023) showed that A92 is highly conserved in GyrA, while alterations in D86 of ParC are common. No GyrA plus ParC alterations caused gepotidacin resistance. MIC determination and genomic surveillance of potential antimicrobial resistance determinants are imperative.
Leveraging artificial intelligence to summarize abstracts in lay language for increasing research accessibility and transparency
Authors: Shyr Cathy , Grout Randall W , Kennedy Nan , Akdas Yasemin , Tischbein Maeve , Milford Joshua , Tan Jason , Quarles Kaysi , Edwards Terri L , Novak Laurie L , White Jules , Wilkins Consuelo H , Harris Paul A
Published: July 2024

Objective

Returning aggregate study results is an important ethical responsibility to promote trust and inform decision making, but the practice of providing results to a lay audience is not widely adopted. Barriers include significant cost and time required to develop lay summaries and scarce infrastructure necessary for returning them to the public. Our study aims to generate, evaluate, and implement ChatGPT 4 lay summaries of scientific abstracts on a national clinical study recruitment platform, ResearchMatch, to facilitate timely and cost-effective return of study results at scale.

Materials and Methods

We engineered prompts to summarize abstracts at a literacy level accessible to the public, prioritizing succinctness, clarity, and practical relevance. Researchers and volunteers assessed ChatGPT-generated lay summaries across five dimensions: accuracy, relevance, accessibility, transparency, and harmfulness. We used precision analysis and adaptive random sampling to determine the optimal number of summaries for evaluation, ensuring high statistical precision.

Results

ChatGPT achieved 95.9% (95% CI, 92.1–97.9) accuracy and 96.2% (92.4–98.1) relevance across 192 summary sentences from 33 abstracts based on researcher review. 85.3% (69.9–93.6) of 34 volunteers perceived ChatGPT-generated summaries as more accessible and 73.5% (56.9–85.4) more transparent than the original abstract. None of the summaries were deemed harmful. We expanded ResearchMatch’s technical infrastructure to automatically generate and display lay summaries for over 750 published studies that resulted from the platform’s recruitment mechanism.

Discussion and Conclusion

Implementing AI-generated lay summaries on ResearchMatch demonstrates the potential of a scalable framework generalizable to broader platforms for enhancing research accessibility and transparency.
Barriers and facilitators to the uptake of electronic collection and use of patient-reported measures in routine care of older adults: a systematic review with qualitative evidence synthesis
Authors: Hettiarachchi Senarath Gayanika M , Delir Haghighi Pari , Bai Lu , Shannon Michelle M , Andrew Nadine E , Srikanth Velandai , Snowdon David A , O’Connor Denise A
Published: July 2024

Objective

The aims of this systematic review were to (1) synthesize the available qualitative evidence on the barriers and facilitators influencing implementation of the electronic collection and use of patient-reported measures (PRMs) in older adults’ care from various stakeholder perspectives and (2) map these factors to the digital technology implementation framework Non-adoption, Abandonment, challenges to the Scale-up, Spread, Sustainability (NASSS) and behavior change framework Capability, Opportunity, Motivation, Behaviour (COM-B).

Materials and Methods

A search of MEDLINE, CINAHL Plus, and Web of Science databases from 1 January 2001 to 27 October 2021 was conducted and included English language qualitative studies exploring stakeholder perspectives on the electronic collection and use of PRMs in older adults’ care. Two authors independently screened studies, conducted data extraction, quality appraisal using the Critical Appraisal Skills Programme (CASP), data coding, assessed confidence in review findings using Grading of Recommendations Assessment, Development, and Evaluation Confidence in the Evidence from Reviews of Qualitative Research (GRADE CERQual), and mapped the findings to NASSS and COM-B. An inductive approach was used to synthesize findings describing the stakeholder perspectives of barriers and facilitators.

Results

Twenty-two studies were included from the 3368 records identified. Studies explored older adult, caregiver, healthcare professional, and administrative staff perspectives. Twenty nine of 34 review findings (85%) were graded as having high or moderate confidence. Key factors salient to older adults related to clinical conditions and socio-cultural factors, digital literacy, access to digital technology, and user interface. Factors salient to healthcare professionals related to resource availability to collect and use PRMs, and value of PRMs collection and use.

Conclusion

Future efforts to implement electronic collection and use of PRMs in older adults’ care should consider addressing the barriers, facilitators, and key theoretical domains identified in this review. Older adults are more likely to adopt electronic completion of PRMs when barriers associated with digital technology access, digital literacy, and user interface are addressed. Future research should explore the perspectives of other stakeholders, including those of organizational leaders, digital technology developers and implementation specialists, in various healthcare settings and explore factors influencing implementation of PREMs.

PROSPERO registration number

CRD42022295894
Establishment and activity of the planning and acting network for low dose radiation research in Japan (PLANET): 2016–2023
Authors: Yamada Yutaka , Imaoka Tatsuhiko , Iwasaki Toshiyasu , Kobayashi Junya , Misumi Munechika , Sakai Kazuo , Sugihara Takashi , Suzuki Keiji , Tauchi Hiroshi , Yasuda Hiroshi , Yoshinaga Shinji , Sasatani Megumi , Tanaka Satoshi , Doi Kazutaka , Tomita Masanori , Iizuka Daisuke , Kakinuma Shizuko , Sasaki Michiya , Kai Michiaki
Published: July 2024

The Planning and Acting Network for Low Dose Radiation Research in Japan (PLANET) was established in 2017 in response to the need for an all-Japan network of experts. It serves as an academic platform to propose strategies and facilitate collaboration to improve quantitative estimation of health risks from ionizing radiation at low-doses and low-dose-rates. PLANET established Working Group 1 (Dose-Rate Effects in Animal Experiments) to consolidate findings from animal experiments on dose-rate effects in carcinogenesis. Considering international trends in this field as well as the situation in Japan, PLANET updated its priority research areas for Japanese low-dose radiation research in 2023 to include (i) characterization of low-dose and low-dose-rate radiation risk, (ii) factors to be considered for individualization of radiation risk, (iii) biological mechanisms of low-dose and low-dose-rate radiation effects and (iv) integration of epidemiology and biology. In this context, PLANET established Working Group 2 (Dose and Dose-Rate Mapping for Radiation Risk Studies) to identify the range of doses and dose rates at which observable effects on different endpoints have been reported; Working Group 3 (Species- and Organ-Specific Dose-Rate Effects) to consider the relevance of stem cell dynamics in radiation carcinogenesis of different species and organs; and Working Group 4 (Research Mapping for Radiation-Related Carcinogenesis) to sort out relevant studies, including those on non-mutagenic effects, and to identify priority research areas. These PLANET activities will be used to improve the risk assessment and to contribute to the revision of the next main recommendations of the International Commission on Radiological Protection.
Detection of decreased granules in neutrophils by automated hematology analyzers XR-1000 and UniCel DxH 800
Authors: Kato Yosuke , Sakamoto Daisuke , Ohnishi Hiroaki , Taki Tomohiko
Published: July 2024

Objective

This study aimed to investigate the utility of neutrophil-related cell population data obtained by automated hematology analyzers in assessing myelodysplastic syndrome cases with decreased granules in neutrophils.

Methods

A total of 108 subjects were classified into normal granule (n = 35), hypogranulation (n = 37), or hypergranulation (n = 36) groups. Neutrophil cell area and granule area were measured by ImageJ. All samples were analyzed on the XR-1000 and UniCel DxH 800, and neutrophil-related parameters were compared among the 3 groups.

Results

Neutrophil cell area and the ratio of the granular area showed significant differences among the 3 groups; they were the highest in the hypergranulation group and lowest in the hypogranulation group. XR-1000 data showed significant differences in NE-SFL and NE-FSC among the 3 groups (P < .0001). NE-SFL and NE-FSC discriminated most accurately hypogranulation group against other groups. UniCel DxH 800 data showed significant differences in MN-V-NE, MN-MALS-N, MN-UMALS-NE, SD-UMALS-NE (P <.01), MN-LMALS-NE, and SD-LMALS-NE (P <.05) among the 3 groups. The combination of SD-V-NE and SD-LMALS-NE discriminated most accurately the hypogranulation group against the other groups.

Conclusion

NE-SFL and NE-FSC and the combination of SD-V-NE and SD-LMALS-NE are useful in detecting cases with decreased granules in neutrophils.
Diabetic status and the performances of creatinine- and cystatin C–based eGFR equations
Authors: Delanaye Pierre , Björk Jonas , Vidal-Petiot Emmanuelle , Flamant Martin , Ebert Natalie , Schaeffner Elke , Grubb Anders , Christensson Anders , Nyman Ulf , Stehlé Thomas , Pottel Hans
Published: July 2024

Background

The estimation of glomerular filtration rate (GFR) is one tool to detect renal disease. The most used biomarker remains serum creatinine and the European Kidney Function Consortium (EKFCcrea) equation is the most validated in Europe. More recently, cystatin C has been proposed as a biomarker. We studied the performances of the EKFC equations in a large cohort of subjects according to their diabetic status.

Methods

Four cohorts from the EKFC dataset were retrospectively considered in which the diabetic status was available. GFR was measured by plasma clearances (mGFR; iohexol or chromium 51–ethylenediaminetetraacetic acid). The performance of the equations was assessed by calculating bias, precision [interquartile range (IQR)] and P30 (percentage of eGFR values within ±30% of mGFR).

Results

In the whole population (N = 6158), the median age was 61 years (IQR 47–72) and 45.8% were women. The mean mGFR was 60 ml/min/1.73 m2 (IQR 39–82). Compared with non-diabetic individuals (n = 5124), diabetic patients (n = 1034) were older, more frequently male, heavier and had lower mGFR. The performance of the EKFCcys equation was similar to that of the EKFCcrea equation, but the EKFCcrea+cys equation had a better P30 than the single-biomarker equations. P30 values were substantially lower in diabetic patients than in non-diabetic patients, but according to a matched analysis, this is mainly explained by the difference in GFR levels between the two populations, not by diabetic status.

Conclusion

We showed that the equation combining creatinine and cystatin C performed better. If the accuracy of equations seems better in non-diabetic than in diabetic individuals, it is more likely due to differences in GFR levels rather than diabetic status.
Prevalence of Mycoplasma genitalium Infection and Macrolide and Fluoroquinolone Resistance Mutations Among US Air Force Service Members With HIV, 2016–2020
Authors: Hakre Shilpa , Sanders-Buell Eric , Casimier Rosemary O , O’Sullivan Anne Marie , Peel Sheila A , Tovanabutra Sodsai , Scott Paul T , Okulicz Jason F
Published: July 2024

Background

Mycoplasma genitalium (MG) infection is a public health concern due to antimicrobial resistance (AMR). Data are limited on repeat MG infection and AMR among US Air Force service members with HIV.

Methods

US Air Force service members seeking HIV care were screened for MG infection during the surveillance period (16 May 2016–16 March 2020). Baseline and repeat MG prevalence rates were estimated. An extended Cox proportional hazards regression model evaluated characteristics associated with repeat MG infection. MG-positive rectal samples were tested for macrolide or fluoroquinolone resistance.

Results

Among 299 male patients from a total of 308 patients followed during the surveillance period, baseline prevalence of MG infection was 19.7% (n = 59); among the 101 patients who screened positive for MG at any time during the surveillance period, repeat MG was 35% (n = 36). Characteristics independently associated with increased risk of repeat infection were sexually transmitted infection history vs none (adjusted hazard ratio [aHR], 2.33; 95% CI, 1.26–4.31), a sexually transmitted infection coinfection vs no positive test result in the medical records (aHR, 5.13; 95% CI, 2.78–9.49), and a new HIV diagnosis (<1 vs ≥1 year; aHR, 2.63; 95% CI, 1.45–3.73). AMR in MG-positive rectal specimens was 88% (43/49) indicating macrolide resistance, 18% (10/56) quinolone resistance, and 18% (10/56) both.

Conclusions

Macrolide and fluoroquinolone resistance mutations were common. Testing for co-occurring MG infection and AMR mutations may be warranted in guiding treatment for sexually transmitted infections such as chlamydia or gonorrhea detected at HIV diagnosis.
Development of a major amputation prediction model and nomogram in patients with diabetic foot
Authors: Chen Yi , Zhuang Jun , Yang Caizhe
Published: July 2024

Background

Diabetes mellitus, as one of the world’s fastest-growing diseases, is a chronic metabolic disease that has now become a public health problem worldwide. The purpose of this research was to develop a predictive nomogram model to demonstrate the risk of major amputation in patients with diabetic foot.

Methods

A total of 634 Type 2 Diabetes Mellitus (T2DM) patients with diabetic foot ulcer hospitalized at the Air Force Medical Center between January 2018 and December 2023 were included in our retrospective study. There were 468 males (73.82%) and 166 females (26.18%) with an average age of 61.64 ± 11.27 years and average body mass index of 24.45 ± 3.56 kg/m2. The predictive factors were evaluated by single factor logistic regression and multiple logistic regression and the predictive nomogram was established with these features. Receiver operating characteristic (subject working characteristic curve) and their area under the curve, calibration curve, and decision curve analysis of this major amputation nomogram were assessed. Model validation was performed by the internal validation set, and the receiver operating characteristic curve, calibration curve, and decision curve analysis were used to further evaluate the nomogram model performance and clinical usefulness.

Results

Predictors contained in this predictive model included body mass index, ulcer sites, hemoglobin, neutrophil-to-lymphocyte ratio, blood uric acid (BUA), and ejection fraction. Good discrimination with a C-index of 0.957 (95% CI, 0.931–0.983) in the training group and a C-index of 0.987 (95% CI, 0.969–1.000) in the validation cohort were showed with this predictive model. Good calibration were displayed. The decision curve analysis showed that using the nomogram prediction model in the training cohort and validation cohort would respectively have clinical benefits.

Conclusion

This new nomogram incorporating body mass index, ulcer sites, hemoglobin, neutrophil-to-lymphocyte ratio, BUA, and ejection fraction has good accuracy and good predictive value for predicting the risk of major amputation in patients with diabetic foot.
Nutritional guide to feeding wheat and wheat co-products to swine: a review
Authors: Stas Ethan B , DeRouchey Joel M , Goodband Robert D , Tokach Mike D , Woodworth Jason C , Gebhardt Jordan T
Published: July 2024

Inclusion of wheat grain can offer feeding opportunities in swine diets because of its high starch, crude protein (CP), amino acid (AA), and phosphorus (P) content. High concentrations of starch within wheat grain makes it a good energy source for swine. Mean energy content of wheat was 4,900 and 3,785 kcal/kg dry matter (DM) for digestible energy and metabolizable energy, respectively. CP concentration can vary based on the class of wheat which include hard red winter, hard red spring, soft red winter, hard white, soft white, and durum. The average CP of all wheat data collected in this review was 12.6% with a range of 8.5% to 17.6%. The AA concentration of wheat increases with increasing CP with the mean Lys content of 0.38% with a standardized ileal digestibility (SID) of 76.8%. As CP of wheat increases, the SID of AA in wheat also increases. Mean P of wheat was 0.27% and median P was 0.30%. Off-quality wheat is often associated with sprouts, low-test weight, or mycotoxin-contamination. Sprouted and low-test weight wheat are physical abnormalities associated with decreased starch within wheat kernel that leads to reductions in energy. The assumed energy value of wheat grain may need to be reduced by up to 10% when the proportion of sprouted to non-sprouted wheat is up to 40% whereas above 40%, wheat’s energy may need to be reduced by 15% to 20%. Low-test weight wheat appears to not influence pig performance unless it falls below 644 kg/m3 and then energy value should be decreased by 5% compared to normal wheat. Deoxynivalenol (DON) contamination is most common with wheat grain. When content is above the guidance level of 1 mg/kg of DON in the complete diet, each 1 mg/kg increase in a DON-contaminated wheat-based diet will result in a 11% and 6% reduction in ADG and ADFI for nursery pigs, and a 2.7% and 2.6% reduction in ADG and ADFI, in finishing pigs, respectively. Wheat co-products are produced from the flour milling industry. Wheat co-products include wheat bran middlings, millrun, shorts, and red dog. Wheat co-products can be used in swine diets, but application may change because of differences in the final diet energy concentration due to changes in the starch and fiber levels of each wheat co-product. However, feeding wheat co-products are being evaluated to improve digestive health. Overall, wheat and wheat co-products can be fed in all stages of production if energy and other nutrient characteristics are considered.
Long-Term Outcomes Following Inguinal Hernia Repair With Mesh Performed by Medical Doctors and Surgeons in Ghana
Authors: Beard Jessica H. , Ohene-Yeboah Michael , Kasu Emmanuel S. , Affram Nelson , Tabiri Stephen , Amoako Joachim K. A. , Abantanga Francis A. , Löfgren Jenny
Published: July 2024

Objective:

To assess long-term outcomes following inguinal hernia repair with mesh performed by medical doctors and surgeons in Ghana.

Background:

Task sharing of surgical care with nonsurgeons can increase access to essential surgery. Long-term safety and outcomes of task sharing are not well-described for hernia repair.

Methods:

This prospective cohort study was conducted in Ho, Ghana. After completing a training course, 3 medical doctors and 2 surgeons performed inguinal hernia repairs with mesh on men with primary, reducible hernias. The primary outcome of this study was hernia recurrence at 5 years. The noninferiority limit was 5 percentage points. Secondary endpoints included pain and self-assessed health status at 5 years.

Results:

A total of 242 operations in 241 participants were included, including 119 hernia repairs performed by the medical doctors and 123 performed by the surgeons. One hundred and sixty-nine participants (70.1%) were seen in follow-up at 5 years, 29 participants (12.0%) had died and 43 (17.8%) were lost to follow-up. The overall 5-year recurrence rate was 4.7% (n = 8). The absolute difference in recurrence rate between the medical doctor group (2 [2.3%]) and the surgeon group (6 [7.3%]) was −5.0 (1-tailed 95% confidence interval, −10.5; P = 0.06), demonstrating noninferiority of the medical doctors. Participants experienced improvements in groin pain and self-assessed health status that persisted at 5 years.

Conclusions:

Long-term outcomes of elective mesh inguinal hernia repair in men performed by medical doctors and surgeons in Ghana were excellent. Task sharing is a critical tool to address the substantial morbidity of unmet hernia surgery needs in Ghana.
The Influence of Asymmetric Hearing Loss on Peripheral and Central Auditory Processing Abilities in Patients With Vestibular Schwannoma
Authors: Svobodová Veronika , Profant Oliver , Syka Josef , Tóthová Diana , Bureš Zbyněk
Published: July 2024

Objectives:

Asymmetric or unilateral hearing loss (AHL) may cause irreversible changes in the processing of acoustic signals in the auditory system. We aim to provide a comprehensive view of the auditory processing abilities for subjects with acquired AHL, and to examine the influence of AHL on speech perception under difficult conditions, and on auditory temporal and intensity processing.

Design:

We examined peripheral and central auditory functions for 25 subjects with AHL resulting from vestibular schwannoma, and compared them to those from 24 normal-hearing controls that were matched with the AHL subjects in mean age and hearing thresholds in the healthy ear. Besides the basic hearing threshold assessment, the tests comprised the detection of tones and gaps in a continuous noise, comprehension of speech in babble noise, binaural interactions, difference limen of intensity, and detection of frequency modulation. For the AHL subjects, the selected tests were performed separately for the healthy and diseased ear.

Results:

We observed that binaural speech comprehension, gap detection, and frequency modulation detection abilities were dominated by the healthy ear and were comparable for both groups. The AHL subjects were less sensitive to interaural delays, however, they exhibited a higher sensitivity to sound level, as indicated by lower difference limen of intensity and a higher sensitivity to interaural intensity difference. Correlations between the individual test scores indicated that speech comprehension by the AHL subjects was associated with different auditory processing mechanisms than for the control subjects.

Conclusions:

The data suggest that AHL influences both peripheral and central auditory processing abilities and that speech comprehension under difficult conditions relies on different mechanisms for the AHL subjects than for normal-hearing controls.
Anterior Iliac Crest Bone Graft Harvest Using Acetabular Reamers
Authors: Page Brian J. , Ricci William M.
Published: July 2024

A 67-year-old man with a recalcitrant tibia nonunion with implant failure is presented. Treatment was a single-stage nonunion repair with dual-plating and anterior iliac crest bone graft using acetabular reamers. The technical aspects of acetabular reamer for iliac crest bone graft harvest and the principles of nonunion repair are discussed.

Video available at:

https://ota.org/education/ota-online-resources/video-library-procedures-techniques/anterior-iliac-crest-bone-0
Indocyanine Green–Based Fluorescence Imaging to Guide Local Tissue Rearrangement of a Complex Morel–Lavallee Lesion About a Hip: A Technical Trick
Authors: Post Joel M. , Hauch Adam , Trinh Alan
Published: July 2024

Morel–Lavellee (ML) lesions are challenging injuries that can be complicated by persistent fluid collection and superimposed infection. The use of indocyanine green (ICG)–based fluorescence in orthopedic trauma continues to advance. ICG can be used to assess tissue perfusion and guide local tissue rearrangement. Perforating vessels can be easily identified and protected without the use of microvascular techniques, which can augment traditional keystone island perforator flap techniques. This case presentation and accompanied video demonstrate the use of ICG-based fluorescence to guide local tissue rearrangement to successfully treat an infected complex Morel–Lavellee lesion about a hip.

Video available at:

https://ota.org/education/ota-online-resources/video-library-procedures-techniques/icg-based-fluorescence-imaging
Update of antibody–drug conjugates for hematological malignancies
Authors: Sun Wenyue , Hu Shunfeng , Wang Xin
Published: July 2024

Purpose of review

Antibody–drug conjugates (ADCs), consisting of monoclonal antibodies (mAbs) covalently linked to cytotoxic drugs via chemical linkers, are a kind of promising tumor immunotherapy. ADCs also face a number of challenges, including unavoidable adverse effects, drug resistance, tumor targeting and payload release. To address these issues, in addition to optimizing the individual components of ADCs, such as new payloads, linkage sites and new targets, and using bispecific antibodies to increase precision, attention should be paid to optimizing the dosage of ADCs.

Recent findings

There are currently 7 ADCs approved for marketing by the Food and Drug Administration (FDA) for hematological malignancies, and dozens of other ADCs are either in clinical trials or in the process of applying for marketing. In recent clinical studies targeting ADCs in hematologic malignancies, in addition to validating effectiveness in different indications, researchers have attempted to combine ADCs with other chemotherapeutic agents in anticipation of increased therapeutic efficacy. Furthermore, the availability of bispecific antibodies may increase the safety and efficacy of ADCs.

This review summarized the progress of research on ADCs in hematological malignancies, the challenges being faced, and possible future directions to improve the efficacy of ADCs, which can provide novel insight into the future exploration of ADCs in the treatment of hematological malignancies.
The evolution of molecular management of carcinoma of unknown primary
Authors: Sivakumaran Tharani , Tothill Richard W. , Mileshkin Linda R.
Published: July 2024

Purpose of review

There is significant need to improve diagnostic and therapeutic options for patients with cancer of unknown primary (CUP). In this review, we discuss the evolving landscape of molecular profiling in CUP.

Recent findings

Molecular profiling is becoming accepted into the diagnostic work-up of CUP patients with tumour mutation profiling now described in international CUP guidelines. Although tissue-of-origin (ToO) molecular tests utilising gene-expression and DNA methylation have existed some time, their clinical benefit remains unclear. Novel technologies utilising whole genome sequencing and machine learning algorithms are showing promise in determining ToO, however further research is required prior to clinical application. A recent international clinical trial found patients treated with molecularly-guided therapy based on comprehensive-panel DNA sequencing had improved progression-free survival compared to chemotherapy alone, confirming utility of performing genomic profiling early in the patient journey. Small phase 2 trials have demonstrated that some CUP patients are responsive to immunotherapy, but the best way to select patients for treatment is not clear.

Management of CUP requires a multifaceted approach incorporating clinical, histopathological, radiological and molecular sequencing results to assist with identifying the likely ToO and clinically actionable genomic alternations. Rapidly identifying a subset of CUP patients who are likely to benefit from site specific therapy, targeted therapy and/or immunotherapy will improve patient outcomes.
The role of signaling lymphocyte activation molecule family receptors in hematologic malignancies
Authors: Kwantwi Louis Boafo , Rosen Steven T. , Querfeld Christiane
Published: July 2024

Purpose of review

In this review, we provide an overview of the current understanding of SLAM-family receptors in hematologic malignancies. We highlighted their contribution to the disease pathogenesis and targeting strategies to improve therapeutic outcomes.

Recent findings

Emerging studies have reported the tumor-promoting role of SLAM-family receptors in various hematologic malignancies, including chronic lymphocytic leukemia, acute myeloid leukemia, and multiple myeloma. Specifically, they regulate the interaction between malignant cells and the tumor microenvironment to promote apoptosis resistance, therapeutic resistance, impairment of antitumor and tumor progression.

SLAM-family receptors promote the progression of hematologic malignancies by regulating the interaction between malignant cells and the tumor microenvironment. This provides the rationale that SLAM-targeted therapies are appealing strategies to enhance therapeutic outcomes in patients.
Potential application of artificial intelligence in cancer therapy
Authors: Riaz Irbaz Bin , Khan Muhammad Ali , Haddad Tufia C.
Published: July 2024

Purpose of review

This review underscores the critical role and challenges associated with the widespread adoption of artificial intelligence in cancer care to enhance disease management, streamline clinical processes, optimize data retrieval of health information, and generate and synthesize evidence.

Recent findings

Advancements in artificial intelligence models and the development of digital biomarkers and diagnostics are applicable across the cancer continuum from early detection to survivorship care. Additionally, generative artificial intelligence has promised to streamline clinical documentation and patient communications, generate structured data for clinical trial matching, automate cancer registries, and facilitate advanced clinical decision support. Widespread adoption of artificial intelligence has been slow because of concerns about data diversity and data shift, model reliability and algorithm bias, legal oversight, and high information technology and infrastructure costs.

Artificial intelligence models have significant potential to transform cancer care. Efforts are underway to deploy artificial intelligence models in the cancer practice, evaluate their clinical impact, and enhance their fairness and explainability. Standardized guidelines for the ethical integration of artificial intelligence models in cancer care pathways and clinical operations are needed. Clear governance and oversight will be necessary to gain trust in artificial intelligence-assisted cancer care by clinicians, scientists, and patients.
Treatment approaches for older Hodgkin lymphoma patients
Authors: Bröckelmann Paul J.
Published: July 2024

Purpose of review

Hodgkin lymphoma (HL) occurs at two age peaks around 25 and 60 years of age. Due to varying fitness and co-morbidities older patients are a heterogeneous group that has relatively poor treatment outcomes. The evolving therapeutic landscape for older HL is summarized herein.

Recent findings

Due to lack of data from larger trials and approval of novel drugs, first-line treatment of limited-stage HL (i.e. early-stage favourable and unfavourable) remains largely A(B)VD and radiotherapy based. For patients with advanced-stage HL, the anti-CD30 antibody-drug conjugate brentuximab vedotin is approved in combination with AVD chemotherapy (BV-AVD). Due to toxicities such as febrile neutropenia or polyneuropathy and lack of improvement in progression-free and overall survival in the older subgroup, fully concomitant BV-AVD is however not used widely. More recently, promising early data was reported with the combination of nivolumab and AVD (N-AVD) in patients >60 years with advanced-stage HL. Second-line treatment depends on fitness and might include high-dose chemotherapy and autologous stem-cell transplantation for selected patients. For unfit or multiply relapsed patients, anti-PD1 antibodies are the preferred treatment option.

The increasing number of older HL patients constitutes a therapeutic challenge despite recent advances and the increased usage of targeted agents.
Cutaneous Involvement by Refractory Celiac Disease Type 2 Histologically Mimicking Mycosis Fungoides
Authors: Mei Angela , Allanson Benjamin , Hall Dustin , Ardakani Nima Mesbah , Harvey Nathan Tobias
Published: July 2024

Refractory celiac disease (RCD) is a rare condition characterized by persistent malabsorptive symptoms and villous atrophy despite a gluten-free diet. While RCD type 1 has a normal intraepithelial lymphocyte phenotype, RCD type 2 is defined by the presence of immunophenotypically aberrant and monoclonal intraepithelial T lymphocytes, with a high propensity to transform to enteropathy-associated T-cell lymphoma (EATL). Although dermatological manifestations of celiac disease are common, presentation with cutaneous involvement by abnormal lymphocytes of RCD type 2 or EATL is rare, with few histologic descriptions in the literature. We describe the case of a 66-year-old man with a history of celiac disease presenting with a generalized, erythematous papular rash over his torso, upper arms, and legs. Biopsy of his skin lesions showed prominent hyperkeratosis with underlying spongiosis and interface change. Increased intraepithelial (epidermotropic) lymphocytes were observed, out of proportion to the level of spongiosis, but not overly atypical in appearance. Immunohistochemistry revealed an aberrant T-cell immunophenotype (CD3/2/7 positive; CD5/4/8 negative), raising suspicion for a cutaneous T-cell lymphoproliferative disorder. A duodenal biopsy demonstrated total villous atrophy with a morphologically bland population of epitheliotropic T lymphocytes showing the same aberrant immunophenotype. Similar cells were also identified by flow cytometry in the peripheral blood. In conjunction with the history of celiac disease, a diagnosis of RCD type 2 or ‘EATL in situ’ with cutaneous involvement was made. Cutaneous RCD type 2 or EATL should be considered as differential diagnoses in patients with a history of celiac disease and histopathology reminiscent of epidermotropic forms of cutaneous T-cell lymphoma.
Malignant Dendritic Cell Sarcomas in the Skin: 2 Cases of Rare Sarcoma Subtypes With Literature Review
Authors: Mehta Apoorva , Luyten Sophia , Abdulhak Abraham , Mahmud Haseeb , Gillen William , Gru Alejandro A.
Published: July 2024

Interdigitating dendritic cell sarcoma is a rare, aggressive hematological malignancy primarily originating in lymph nodes, with only 10 reported cases presenting in the skin (primary cutaneous interdigitating dendritic cell sarcoma). Past presentations showed erythematous nodules on the proximal extremities, back, or face. Morphologically, these neoplasms are similar to melanomas and other dendritic cell (DC) tumors, making their diagnosis difficult. Here, we present 1 case of primary cutaneous interdigitating dendritic cell sarcomas and another 1 of malignant indeterminate dendritic cell tumor (indeterminate DC sarcoma). The first case is an 83-year-old man who presented with recent ulceration and bleeding of an asymptomatic, slow growing lesion on his right thigh with biopsy revealing a large, well-circumscribed polypoid spindle cell tumor in the dermis with atypical cells with vesicular nuclei in a lymphoplasmacytic background and immunohistochemistry positivity for CD45, CD68, S100, and Cyclin D1. The second case is a 74-year-old man who presented with a progressively darkening and enlarging abdominal skin lesion with biopsy revealing a diffuse infiltrate of atypical poorly differentiated pleomorphic nuclear cells and immunohistochemistry positivity for S100, CD1a, CD56, CD43, cyclin D1, CD31, CD4, and BRAF V600E. Our findings contribute to expand the reported literature on primary cutaneous DC sarcomas.
Hyaluronic Acid Filler Longevity in the Mid-face: A Review of 33 Magnetic Resonance Imaging Studies
Authors: Master Mobin , Azizeddin Arshia , Master Vahid
Published: July 2024

Background:

Recent evidence challenges the conventional belief that hyaluronic acid (HA) fillers have a short lifespan of 3–12 months. This study, using extensive patient data and long-term imaging post-injection, suggests a need to reconsider refilling protocols and underscores the critical role of precise clinical photography for accurate comparisons.

Methods:

The study enrolled 33 patients who received HA fillers in the mid-face, excluding those with recent injections, permanent fillers, or specific medical histories. Magnetic resonance imaging (MRI) was conducted on 24 asymptomatic and nine edema-concerned patients over 2.5 years. Two blinded radiologists assessed filler presence and longevity based on requested MRI observations.

Results:

MRI scans confirmed HA presence in all 33 patients, with no complete dissipation observed over a 2-year period post injection. Among them, 21 had not received injections for 2–5 years, 12 for over 5 years, and some for up to 8–15 years. Varying volumes of HA were noted: mild in nine patients, moderate in 13, and severe in 11. The study reported HA longevity of up to 15 years across different products, with a 95% confidence interval of 84.47% ± 4.43%, demonstrating the persistence of cross-linked HA fillers in the mid-face.

Conclusions:

HA fillers remained detectable for at least 2 years in all 33 patients, with one patient showing filler longevity of up to 15 years. These findings suggest significant implications for filler management practices. Further research with larger cohorts and ongoing imaging follow-up is warranted to fully understand HA filler longevity and optimize clinical protocols.
Lack of Acute Agomelatine Effect in a Model of Social Anxiety in Healthy Volunteers
Authors: dos Santos Rafael G. , da Silva Dias Isabella C. , Zuardi Antonio W. , Queiroz Regina H. C. , Guimarães Francisco S. , Hallak Jaime E. C. , Crippa José Alexandre S.
Published: July 2024

Background

Agomelatine is an antidepressant drug that acts as an agonist of melatoninergic MT1/2 receptors and an antagonist of serotonergic 5-HT2C receptors. Studies suggest that agomelatine has anxiolytic properties in social anxiety, but there are no studies that assessed the effects of this compound in human experimental anxiety induced by a public speaking test. The objective of our investigation was to assess the effects of agomelatine on human experimental anxiety using the Simulation Public Speaking Test (SPST).

Methods

Agomelatine (25 mg, n = 14), citalopram (20 mg, n = 14), venlafaxine (75 mg, n = 14), or placebo (n = 14) were administered in single doses to healthy volunteers in a double-blind study. Subjective anxiety was assessed with the Visual Analogue Mood Scale. Arterial blood pressure, heart rate, and blood levels of prolactin and cortisol were also recorded, as well as plasma levels of the 3 drugs.

Results

The SPST induced significant subjective, physiological, and hormonal effects in all groups. The SPST also increased the anxiety and decreased mental sedation Visual Analogue Mood Scale factors during the anticipatory and performance phases of the test. Citalopram increased anxiety during the test in females, whereas agomelatine and venlafaxine were not different from placebo.

Conclusions

Confirming previous results, a serotonin selective reuptake inhibitor, citalopram, caused an anxiogenic effect in the SPST only in females. Acute administration of a low dose of agomelatine failed to modify the behavioral and physiological changes caused by this test. Future studies using higher doses and repeated administration should investigate if agomelatine behavioral and physiological effects could be detected in human experimental anxiety models.