bluuebunny/crossref_metadata_2025_split huggingface dataset:
Use of Intravenous Acyclovir for Prophylaxis of Cytomegalovirus Infection in Renal Transplant Recipients
Authors: Sturgill Marc G. , Hatton Jimmi 
Published: April 2023

Objective To review the incidence and risk factors for cytomegalovirus (CMV) infection and disease following renal transplantation, and the use of intravenous acyclovir for infection prophylaxis. Data Sources An English-language literature search using MEDLINE (1982–93), Index Medicus (1982–93), and bibliographic reviews of related textbooks and review articles. Study Selection One hundred forty-five articles were selected. Articles were assessed for study quality and specific information addressing the stated purpose. In articles reporting the results of clinical trials, emphasis was placed on comparative pharmacokinetic parameters, efficacy, and toxicity. Synthesis A review of human trials suggests that acyclovir is effective for prevention of CMV infection and disease following renal transplantation. When compared with active or passive CMV immunization, ganciclovir, and foscamet sodium, acyclovir appears to exhibit the most favorable combination of safety and efficacy in the renal transplant population. However, the optimal dose of intravenous acyclovir when compared with oral administration is not clearly established. Conclusions Acyclovir will continue to be widely used for CMV prophylaxis following renal transplantation. Postoperative complications often require the use of intravenous medications, and the optimal dosing schedule for intravenous acyclovir in this population is an issue that needs to be addressed. A randomized, concentration-controlled clinical trial may be the best approach to establish a safe and effective dosing schedule for intravenous acyclovir administration in the renal transplant population.
Sumatriptan: A New Treatment for Migraine and Cluster Headaches
Authors: Ross Mary B. , Mulcahy Michelle M. , Mutnick Alan H. 
Published: April 2023

Objective To provide an overview of the pharmacology, pharmacokinetics, clinical trials, adverse drug reactions, and dosing recommendations for sumatriptan, a new agent for treating migraine headaches. Data Sources Information was collected by conducting a MEDLINE search for clinical trials, reviews, and other articles dealing with the use of sumatriptan in the treatment of migraine and/or cluster headache. Study Selection Clinical studies, review articles, and editorials were selected for review if they addressed the clinical use, pharmacokinetic profile, adverse drug reaction profile, and dosing recommendations for sumatriptan. Data Extraction Data were used from clinical trials and reviews when the information was obtainable from multiple sources. Data Synthesis Sumatriptan is a serotonin-selective receptor agonist approved by the Food and Drug Administration for the acute treatment of migraine headaches. Clinical trials have reported that sumatriptan is very effective in the rapid reversal of acute migraine headaches. The drug is not without adverse effects and must be used cautiously in patients with ischemic heart disease and coronary vasospasm. In addition, nausea, dizziness, malaise, and fatigue have been reported with sumatriptan's use. Conclusions Sumatriptan may have a significant impact on the lives of patients with migraine headaches. However, because no other serotonin agonists have been released for treating migraine, it will be important that pharmacy personnel have a clear understanding of the uses, adverse effects, administration guidelines, and costs associated with sumatriptan. This will allow pharmacy personnel to educate patients on sumatriptan to ensure the most positive outcomes possible.
Minocycline Treatment for a Methicillin-Resistant Staphylococcus aureus Wound Infection
Authors: Sofia Robert D. , Swanson Keith A. , Sivaprassad R. 
Published: April 2023

Objective To report a case illustrating the possible role of minocycline for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Case Summary Following revision of a total hip replacement, an elderly patient developed an abscess at the site of the surgical wound infection. Initial cultures were positive for multiple organisms indicating colonization. One week after admission, MRSA was cultured from the wound and was thought to represent an infection rather than colonization. The isolate was sensitive to vancomycin, but was resistant to all other routinely tested antistaphylococcal antibiotics. Minocycline 100 mg orally twice daily and topical mupirocin 2.0% ointment applied with dressing changes every 3 days was used to treat the infection after the patient refused placement of the central venous catheter needed for intravenous vancomycin therapy. Following 15 days of minocycline and mupirocin therapy, repeat cultures were positive only for non-group D, alpha-hemolytic streptococci, which was believed to represent colonization of the site. Discussion A brief review of the literature concerning minocycline activity against staphylococcal infections suggests a possible role for minocycline in the treatment of MRSA infections. Case studies illustrating clinical response of MRSA infections to minocycline in various types of combination therapy are reviewed and discussed. The potential link is suggested between minocycline plus mupirocin therapy and the clearance of MRSA from wound cultures in the case presented. Conclusions A possible role of minocycline plus mupirocin for treating non-systemic MRSA infection is suggested by results found in this case. Although they might offer an attractive alternative to intravenous vancomycin therapy, the use of minocycline and topical mupirocin require additional study before they can be routinely recommended for the treatment of MRSA infections.
Intrathecal Baclofen Effective in Treating Spasticity
Authors: Wong Wai-Yip , Hart Linda L. 
Published: April 2023

Objective To provide an overview of the chemistry, adverse-effect profile, and risk-benefit issues of intrathecal administration of baclofen in treating spasticity. Data Sources Information was collected by conducting a MEDLINE search for clinical trials, reviews, and other articles pertaining to the use of intrathecal baclofen. Study Selection Studies, review articles, and editorials that addressed the chemistry, clinical use, and risk-benefit issues of intrathecal baclofen were reviewed. Data Extraction Data were extracted from clinical trials, reviews, and editorials when the information pertained to the purpose of the objective. Data Synthesis Baclofen is a GABAB-receptor agonist that has presynaptic and postsynaptic inhibitory action. Intrathecal administration of baclofen is a rational approach to delivering the drug directly to the GABAB receptors in the spinal cord. The literature demonstrates that long-term intrathecal baclofen administration via a programmable infusion pump is effective in the management of spasticity. Complications of delivering baclofen intrathecally via an infusion pump include pump failure, catheter dislocation, and infection related to the initial procedure or to pump refills. Dosage requirements increase over time as tolerance to baclofen develops. Tolerance is not a serious concern because the dosage requirement is maximized in about one year. Conclusions In treating intractable spasticity, intrathecal baclofen is a viable, safe alternative to destructive surgical neurectomy, which carries risks of serious neurologic complications. Long-term intrathecal baclofen treatment via an implanted programmable infusion pump not only is effective in treating spasticity, but also improves functional capacities in patients who are unresponsive to high-dose oral antispastic agents.
Germanium Use and Associated Adverse Effects: A Review
Authors: Ohri Linda K. , Vicari Susan M. , Malone Patrick M. 
Published: April 2023

Objective To review the trace element germanium, including its use as a nutritional supplement, the published medical research on potential therapeutic applications, and its potential toxicity. The case report and review literature regarding nephrotoxicity are addressed. Data Sources Relevant English-language articles were identified from a MEDLINE, EMBASE, and BIOSIS search using the primary search term germanium. Additional references were identified from the bibliographies of these articles. Study Selection/Data Extraction The main details of the case report and review literature were covered. The reader is referred to review articles as well as case reports for in-depth reviews of the case reports evaluated. Data Synthesis Germanium products are being sold in the US as nutritional supplements for a variety of unproven indications. Published medical research has not clearly substantiated a place for germanium as established drug therapy. Substantial evidence exists associating chronic germanium use with nephrotoxicity. Conclusions Pharmacists and other healthcare practitioners should question patients on their use of nutritional supplements, including germanium, when conducting medication histories. This is especially important for patients with unexplained renal dysfunction. Pharmacists should consider removing germanium products from stock where it is currently included on inventory.
Therapeutic Applications and Economic Opportunities in the Biotechnologic Pharmaceutical Industry
Authors: Wertheimer Albert I. , Grumer Sondra 
Published: April 2023

Objective To discuss the expected future development and implications of the US biotechnologic pharmaceutical industry. Foreign competition and internal forces that might impede the industry are also discussed. Data Sources Searches were conducted in the Business Periodicals Index and the International Pharmaceutical Abstracts databases. Study Selection All studies pertaining to the business of biotechnology were reviewed. Conclusions Biotechnologically produced agents will require a shorter period of development and a less costly production process, and will be generally safer than conventional drugs. Furthermore, these agents will afford superior pharmacotherapy to that of conventional drugs, enhancing the diagnosis and treatment of diseases as harrowing as AIDS and neoplastic disorders.
CNL and aCML should be considered as a single entity based on molecular profiles and outcomes
Authors: Carreño-Tarragona Gonzalo , Álvarez-Larrán Alberto , Harrison Claire , Martínez-Ávila José Carlos , Hernández-Boluda Juan Carlos , Ferrer-Marín Francisca , Radia Deepti H. , Mora Elvira , Francis Sebastian , González-Martínez Teresa , Goddard Kathryn , Pérez-Encinas Manuel , Narayanan Srinivasan , Raya José María , Singh Vikram , Gutiérrez Xabier , Toth Peter , Amat-Martínez Paula , Mcilwaine Louisa , Alobaidi Magda , Mayani Karan , McGregor Andrew , Stuckey Ruth , Psaila Bethan , Segura Adrián , Alvares Caroline , Davidson Kerri , Osorio Santiago , Cutting Robert , Sweeney Caroline P. , Rufián Laura , Moreno Laura , Cuenca Isabel , Smith Jeffery , Morales María Luz , Gil-Manso Rodrigo , Koutsavlis Ioannis , Wang Lihui , Mead Adam J. , Rozman María , Martínez-López Joaquín , Ayala Rosa , Cross Nicholas C. P. 
Published: April 2023

Abstract
Chronic neutrophilic leukemia (CNL) and atypical chronic myeloid leukemia (aCML) are rare myeloid disorders that are challenging with regard to diagnosis and clinical management. To study the similarities and differences between these disorders, we undertook a multicenter international study of one of the largest case series (CNL, n = 24; aCML, n = 37 cases, respectively), focusing on the clinical and mutational profiles (n = 53 with molecular data) of these diseases. We found no differences in clinical presentations or outcomes of both entities. As previously described, both CNL and aCML share a complex mutational profile with mutations in genes involved in epigenetic regulation, splicing, and signaling pathways. Apart from CSF3R, only EZH2 and TET2 were differentially mutated between them. The molecular profiles support the notion of CNL and aCML being a continuum of the same disease that may fit best within the myelodysplastic/myeloproliferative neoplasms. We identified 4 high-risk mutated genes, specifically CEBPA (β = 2.26, hazard ratio [HR] = 9.54, P = .003), EZH2 (β = 1.12, HR = 3.062, P = .009), NRAS (β = 1.29, HR = 3.63, P = .048), and U2AF1 (β = 1.75, HR = 5.74, P = .013) using multivariate analysis. Our findings underscore the relevance of molecular-risk classification in CNL/aCML as well as the importance of CSF3R mutations in these diseases.
meth-SemiCancer: a cancer subtype classification framework via semi-supervised learning utilizing DNA methylation profiles
Authors: Choi Joung Min , Park Chaelin , Chae Heejoon 
Published: April 2023

Abstract
Background
Identification of the cancer subtype plays a crucial role to provide an accurate diagnosis and proper treatment to improve the clinical outcomes of patients. Recent studies have shown that DNA methylation is one of the key factors for tumorigenesis and tumor growth, where the DNA methylation signatures have the potential to be utilized as cancer subtype-specific markers. However, due to the high dimensionality and the low number of DNA methylome cancer samples with the subtype information, still, to date, a cancer subtype classification method utilizing DNA methylome datasets has not been proposed.

Results
In this paper, we present meth-SemiCancer, a semi-supervised cancer subtype classification framework based on DNA methylation profiles. The proposed model was first pre-trained based on the methylation datasets with the cancer subtype labels. After that, meth-SemiCancer generated the pseudo-subtypes for the cancer datasets without subtype information based on the model’s prediction. Finally, fine-tuning was performed utilizing both the labeled and unlabeled datasets.

Conclusions
From the performance comparison with the standard machine learning-based classifiers, meth-SemiCancer achieved the highest average F1-score and Matthews correlation coefficient, outperforming other methods. Fine-tuning the model with the unlabeled patient samples by providing the proper pseudo-subtypes, encouraged meth-SemiCancer to generalize better than the supervised neural network-based subtype classification method. meth-SemiCancer is publicly available at https://github.com/cbi-bioinfo/meth-SemiCancer.
Genome-wide identification and molecular characterization of CRK gene family in cucumber (Cucumis sativus L.) under cold stress and sclerotium rolfsii infection
Authors: Nanda Satyabrata , Rout Priyadarshini , Ullah Ikram , Nag Swapna Rani , Reddy Velagala Veerraghava , Kumar Gagan , Kumar Ritesh , He Shuilian , Wu Hongzhi 
Published: April 2023

Abstract
Background
The plant cysteine-rich receptor-like kinases (CRKs) are a large family having multiple roles, including defense responses under both biotic and abiotic stress. However, the CRK family in cucumbers (Cucumis sativus L.) has been explored to a limited extent. In this study, a genome-wide characterization of the CRK family has been performed to investigate the structural and functional attributes of the cucumber CRKs under cold and fungal pathogen stress.

Results
A total of 15 C. sativus CRKs (CsCRKs) have been characterized in the cucumber genome. Chromosome mapping of the CsCRKs revealed that 15 genes are distributed in cucumber chromosomes. Additionally, the gene duplication analysis of the CsCRKs yielded information on their divergence and expansion in cucumbers. Phylogenetic analysis divided the CsCRKs into two clades along with other plant CRKs. Functional predictions of the CsCRKs suggested their role in signaling and defense response in cucumbers. The expression analysis of the CsCRKs by using transcriptome data and via qRT-PCR indicated their involvement in both biotic and abiotic stress responses. Under the cucumber neck rot pathogen, Sclerotium rolfsii infection, multiple CsCRKs exhibited induced expressions at early, late, and both stages. Finally, the protein interaction network prediction results identified some key possible interacting partners of the CsCRKs in regulating cucumber physiological processes.

Conclusions
The results of this study identified and characterized the CRK gene family in cucumbers. Functional predictions and validation via expression analysis confirmed the involvement of the CsCRKs in cucumber defense response, especially against S. rolfsii. Moreover, current findings provide better insights into the cucumber CRKs and their involvement in defense responses.
Researchers in rheumatology should avoid categorization of continuous predictor variables
Authors: Salis Zubeyir , Gallego Blanca , Sainsbury Amanda 
Published: April 2023

AbstractBackgroundRheumatology researchers often categorize continuous predictor variables. We aimed to show how this practice may alter results from observational studies in rheumatology.MethodsWe conducted and compared the results of two analyses of the association between our predictor variable (percentage change in body mass index [BMI] from baseline to four years) and two outcome variable domains of structure and pain in knee and hip osteoarthritis. These two outcome variable domains covered 26 different outcomes for knee and hip combined. In the first analysis (categorical analysis), percentage change in BMI was categorized as ≥ 5% decrease in BMI, < 5% change in BMI, and ≥ 5% increase in BMI, while in the second analysis (continuous analysis), it was left as a continuous variable. In both analyses (categorical and continuous), we used generalized estimating equations with a logistic link function to investigate the association between the percentage change in BMI and the outcomes.ResultsFor eight of the 26 investigated outcomes (31%), the results from the categorical analyses were different from the results from the continuous analyses. These differences were of three types: 1) for six of these eight outcomes, while the continuous analyses revealed associations in both directions (i.e., a decrease in BMI had one effect, while an increase in BMI had the opposite effect), the categorical analyses showed associations only in one direction of BMI change, not both; 2) for another one of these eight outcomes, the categorical analyses suggested an association with change in BMI, while this association was not shown in the continuous analyses (this is potentially a false positive association); 3) for the last of the eight outcomes, the continuous analyses suggested an association of change in BMI, while this association was not shown in the categorical analyses (this is potentially a false negative association).ConclusionsCategorization of continuous predictor variables alters the results of analyses and could lead to different conclusions; therefore, researchers in rheumatology should avoid it.
Symptoms and signs of urogenital cancer in primary care
Authors: Holtedahl Knut , Borgquist Lars , Donker Gé A. , Buntinx Frank , Weller David , Campbell Christine , Månsson Jörgen , Hammersley Victoria , Braaten Tonje , Parajuli Ranjan 
Published: April 2023

Abstract
Background
Urogenital cancers are common, accounting for approximately 20% of cancer incidence globally. Cancers belonging to the same organ system often present with similar symptoms, making initial management challenging. In this study, 511 cases of cancer were recorded after the date of consultation among 61,802 randomly selected patients presenting in primary care in six European countries: a subgroup analysis of urogenital cancers was carried out in order to study variation in symptom presentation.

Methods
Initial data capture was by completion of standardised forms containing closed questions about symptoms recorded during the consultation. The general practitioner (GP) provided follow-up data after diagnosis, based on medical record data made after the consultation. GPs also provided free text comments about the diagnostic procedure for individual patients.

Results
The most common symptoms were mainly associated with one or two specific types of cancer: ‘Macroscopic haematuria’ with bladder or renal cancer (combined sensitivity 28.3%), ‘Increased urinary frequency’ with bladder (sensitivity 13.3%) or prostatic (sensitivity 32.1%) cancer, or to uterine body (sensitivity 14.3%) cancer, ‘Unexpected genital bleeding’ with uterine cancer (cervix, sensitivity 20.0%, uterine body, sensitivity 71.4%). ‘Distended abdomen, bloating’ had sensitivity 62.5% (based on eight cases of ovarian cancer). In ovarian cancer, increased abdominal circumference and a palpable tumour also were important diagnostic elements. Specificity for ‘Macroscopic haematuria’ was 99.8% (99.7–99.8). PPV > 3% was noted for ‘Macroscopic haematuria’ and bladder or renal cancer combined, for bladder cancer in male patients. In males aged 55–74, PPV = 7.1% for ‘Macroscopic haematuria’ and bladder cancer. Abdominal pain was an infrequent symptom in urogenital cancers.

Conclusions
Most types of urogenital cancer present with rather specific symptoms. If the GP considers ovarian cancer, increased abdominal circumference should be actively determined. Several cases were clarified through the GP’s clinical examination, or laboratory investigations.
A case of septic shock due to delayed diagnosis of Cryptosporidium infection after liver transplantation
Authors: Tie Xin , Zhang Zhongwei , Zhou Ran , Li Yi , Xu Jinmei , Yin Wanhong 
Published: April 2023

Abstract
Background
Cryptosporidium is recognized as a significant pathogen of diarrhea disease in immunocompromised hosts, and studies have shown that Cryptosporidium infection is high in solid organ transplantation (SOT) patients and often has serious consequences. Because of the lack of specificity of diarrheasymptoms cased by Cryptosporidium infection, it is rarely reported in patients undergoing liver transplantation (LT). It frequently delays diagnosis, coming with severe consequences. In clinical work, diagnosing Cryptosporidium infection in LT patients is also complex but single, and the corresponding anti-infective treatment regimen has not yet been standardized. A rare case of septic shock due to a delayed diagnosis of Cryptosporidium infection after LT and relevant literature are discussed in the passage.

Case presentation
A patient who had received LT for two years was admitted to the hospital with diarrhea more than 20 days after eating an unclean diet. After failing treatment at a local hospital, he was admitted to Intensive Care Unit after going into septic shock. The patient presented hypovolemia due to diarrhea, which progressed to septic shock. The patient's sepsis shock was controlled after receiving multiple antibiotic combinations and fluid resuscitation. However, the persistent diarrhea, as the culprit of the patient's electrolyte disturbance, hypovolemia, and malnutrition, was unsolved. The causative agent of diarrhea, Cryptosporidium infection, was identified by colonoscopy, faecal antacid staining, and blood high-throughput sequencing (NGS). The patient was treated by reducing immunosuppression and Nitazoxanide (NTZ), which proved effective in this case.

Conclusion
When LT patients present with diarrhea, clinicians should consider the possibility of Cryptosporidium infection, in addition to screening for conventional pathogens. Tests such as colonoscopy, stool antacid staining and blood NGS sequencing can help diagnose and treat of Cryptosporidium infection early and avoid serious consequences of delayed diagnosis. In treating Cryptosporidium infection in LT patients, the focus should be on the patient's immunosuppressive therapy, striking a balance between anti-immunorejection and anti-infection should be sought. Based on practical experience, NTZ therapy in combination with controlled CD4 + T cells at 100–300/mm3 was highly effective against Cryptosporidium without inducing immunorejection.