bluuebunny/crossref_metadata_2025 huggingface dataset:
X-ray crystallographic studies of protein-ligand interactions
Authors: Palmer Rex A
Published: November 2023

This chapter is concerned with current methods employed for the X-ray analysis of protein structures complexed with ligands. It deals with the methods used for growing crystals, the background to the use of X-ray intensity data, collection and measurement of the X-ray data, methods for analysing and interpretation of the structures. Whilst emphasis is given to the practical aspect of this type of work, in view of the highly specialized nature of X-ray crystallography it has been felt necessary to provide the reader with a background to the underlying theory. X-ray crystallography is highly computational and a great variety of software is available for performing the various stages of the calculations and graphics display. Some of the software used is specific to local research groups whilst other programmes are widely available and employed world-wide. Those programmes mentioned in the text are readily available and prospective users should have no difficulties obtaining copies complete with instructions. Important Internet addresses are included and major suppliers of specialised equipment are listed. The flow chart in Figure 1 indicates the various stages covered in the chapter.
Kinetics and thermodynamics of protein-protein interactions
Authors: Janin Joel
Published: November 2023

The physical chemistry of non-covalent protein-protein interactions aims to answer some fundamental questions: what is the origin of the affinity which enables biological macromolecules to form stable, complex, self-assemblies; what governs the specificity which makes these assemblies unique; which physical features give them functions that their individual components do not have? Given the ubiquitous character of protein-protein interactions, these questions are relevant to nearly all fields in biology, and they have attracted much interest over the years. An outline of the answer was given long ago by Linus Pauling and Max Delbrück (1):
Analysis and classification of protein-protein interactions from a structural perspective
Authors: Jones Susan , Thornton Janet M
Published: November 2023

Interactions between macromolecules are fundamental to many biological processes. Such interactions are central to the functioning of the vertebrate immune system, enzyme regulation, neurotransmitter release in the nervous system, and cell adhesion. The characterization of the interfaces formed when proteins interact is important if these and other systems are to be fully understood, and if the potential to control these interactions for medical and industrial applications is to be explored. The Brookhaven Protein Data Bank (PDB) (1, 2) now contains the three-dimensional coordinates of more than 12000 structures; an ever-increasing number of which are protein-protein complexes, including: oligomeric proteins; enzyme-inhibitor complexes; and antibody-protein complexes. Their deposition allows the analysis of large numbers of these structures, and such computational studies have provided important overviews of the physical and chemical properties of these associations (see, for example, refs 3-6). Protein-protein complexes with different interaction histories and functions require different modes of interaction. This chapter begins with the classification of these associations, considering functional classes of complexes, permanent and non-obligate complexes, and biological and crystallographic associations. The physical and chemical characteristics of biological associations are then discussed, presenting an overview of the properties favouring associations, namely hydrophobic and electrostatic interactions, and shape complementarity. These are then considered in more detail with reference to computational studies conducted on large data sets of protein complexes.
Functional genomics with yeast
Authors: Delneri Daniela , Oliver Stephen G
Published: November 2023

DNA sequencing and other biological data are accumulating at a vertiginous rate. Within the last 5 years, sequences of 23 prokaryotic genomes, the unicellular eukaryote Saccharomyces cerei1isiae (1), and the metazoan Caenorabditis elegans (2) were completed (Entrcz Genomes at The fission yeast Schizosaccharomyces pombe and the fruitfly Drosophila melanogasterwill be the next eukaryotes to have their genomes sequenced and released by the end of this year. There are about 70 microbial genomes (with sizes between 1.5-5 Mb) whose sequences are in progress. In autumn 1999, the first sequence of a human chromosome arm, 22p, was completed by an international consortium of sequencing centres (3). The Human Genome Project (HGP), which started at the beginning of the 1990s, should be completed in the next 5 years (4). By 2005, about 50years after the landmark paper of Watson and Crick on the structure of DNA (5), the complete description of all the genes contained in human chromosomes will be available. In parallel with the HGP, the mouse genome project has also been undertaken and is expected to be completed by 2008 (6).
Splicing pre-mRNA introns
Authors: Mayes Andrew E , Potashkin Judith A , Beggs Jean D
Published: November 2023

In the late 1970s it was discovered that many eukaryotic genes are interrupted by non-coding sequences (intrans). Since then, various types of intrans have been identified, the mechanisms for their removal have been intensively researched, and the possible reasons for their existence have been the subject of much debate. Introns are normally removed from newly transcribed RNA and the regions present in the mature RNA (exons) are concomitantly joined in a process termed RNA splicing. Three different chemical reactions of RNA splicing are currently known, exemplified by the splicing of 1) group I, 2) group II and nuclear precursor messenger RNA (pre-mRNA), and 3) tRNA introns (1). Genes containing group I intrans are found widely in nature, for instance in the chloroplast and mitochondria of plants, in mitochondria of fungi and other lower eukaryotes, in some eubacteria and bacteriophages. These introns have a characteristic, conserved secondary structure, and are spliced in a guanosine co-factor-dependent process that involves two trans-esterification reactions (2). Group II introns have been found in chloroplast, mitochondrial and some eubacterial genomes. They have a highly conserved secondary and tertiary structure that is distinct from that of group I introns. Group II introns (3) are spliced in how trans-esterification reactions that are very similar to those of pre-mRNA splicing (see below). However, unlike pre-mRNA splicing, which is dependent on a complex RNA- and protein-containing machinery called the spliceosome, some group I and group II introns have the ability to self-splice due to the autocatalytic activity of the RNA itself. In contrast to the first two types of splicing chemistry, tRNA introns are spliced in two distinct protein-catalysed reactions; first the intron is excised by an endonuclease, then the two exons are ligated (4).
RNA editing in Physarum polycephalum
Authors: Gott Jonathan M
Published: November 2023

RNAs synthesized in the mitochondria of the acellular slime mold, Physarum polycephalum, contain nucleotides which are not encoded, at least in the conventional sense, in the genes from which they are transcribed. These differences between the mitochondrial DNA and its mRNA (1–3), tRNA (4) and rRNA (5) products are due to multiple types of RNA editing. This topic has recently been reviewed in some detail (6), so the primary focus of this chapter will be on new developments in the field.
Paramyxovirus RNA polymerase stuttering
Authors: Hausmann StÉphane , Garcin Dominique
Published: November 2023

The concept of RNA editing was introduced in 1986 to describe the post-transcriptional insertion of non-genomically encoded uridylates within the coding region of trypanosome mitochondrial mRNAs, which restores the coding capacity of these genes (1). Many other examples of RNA editing by a variety of mechanisms, including nucleotide insertion, deletion and base substitution, were subsequently found. The term RNA editing now describes a large number of separate processes that produce RNA transcripts whose sequence (and informational capacity) differs from that encoded by the corresponding gene, excluding the alterations produced by splicing or 5’ and 3’ end formation (2–4).
Radioisotopes And Immunoassay
Authors: Bristow Adrian F , Thorpe Robin
Published: November 2023

Immunoassay is the quantitative measurement of a substance of interest (‘analyte’) using antibodies which bind specifically to that analyte. For the rest of this chapter, these two main components of the assay will be referred to as ligand and antibody respectively. In order to perform such an assay, it is necessary to measure the binding of the ligand to the antibody at very low concentrations; this has most commonly been achieved with the use of radioisotopes. The first practical application of the principle was the techniques of radioimmunoassay (RIA), invented by Yalow and Berson in the late 1950s (1), for which the Nobel Prize was subsequently awarded. This technique, and subsequently developed related techniques such as immunoradiometric assays and enzyme-linked immunosorbent assays, have revolutionized the biological sciences. Using these methods the minute quantities found in biological materials of a whole range of analytes such as protein hormones, steroids, viral antigens, cytokines and clotting factors can be accurately measured without relying on difficult and sometimes imprecise measurements based on their biological activities. Indeed, it is hard to overestimate the impact that the development of immunoassays has had on the life sciences.
Federal Regulations On Use Of Radionuclides In The USA
Authors: Hotte Eileen D , Nelson Neal
Published: November 2023

The use of radioactive materials and radiation-emitting devices in the USA is regulated by a number of agencies. In 1967, The World Health Organization re-ported that regulation of devices and materials emitting ionizing radiation was divided among 50 state governments, several city governments, six federal agencies, a Federal Council and a Federal Commission (1). The situation in the early 2000s is not much different. In the USA, regulation is by laws, statutes, standards, regulations and ordinances. Laws are the rules of conduct applied and enforced under the authority of state or federal government. They establish proper, permitted, denied and penalized behaviour and statements of goals or intent (2). Statutes are acts of legislature, administrative regulations or any enactment given the force of law by the state (2).
Web scripting for molecular biologists: An introduction to Perl and XML
Authors: Horton Robert M
Published: November 2023

Computer skills are increasingly important to molecular biologists. Internet literacy is essential for finding references in the literature (see Chapter 1), finding gene sequences from the databases (see Chapter 2), and many other tasks (as described in other chapters). Leaming how web-based programs work can help you to become a more effective user of these resources.
Rapid and Accurate Detection of Marssonina coronariae in Apple Trees using Loop-Mediated Isothermal Amplification (LAMP)
Authors: Zhang Lixia , Peng Lan , Wang Yinghao , Liu Hailong , Xu Liangsheng , Huang Lili
Published: November 2023

Marssonina blotch of apple is a well-known plant disease caused by Marssonina coronariae, which can cause severe economic consequences. Due to the importance of early diagnosis for effective plant disease management, we aimed to develop a loop-mediated isothermal amplification (LAMP) assay that could rapidly detect M. coronariae in apple plants. The ribosomal DNA internal transcribed spacer (rDNA-ITS) sequence of M. coronariae was selected as the target for primer design. Our results showed optimal conditions for the LAMP reaction at 62℃ for 50 min, as indicated by color change and gel electrophoresis. The LAMP assay demonstrated specific discriminatory capability in differentiating M. coronariae from other pathogenic fungi in apple plants. In addition, the sensitivity tests revealed a detection limit of 100 fg μL-1 genomic DNA and 100 spores of M. coronariae for the LAMP assay. Finally, we successfully applied the LAMP assay to detect M. coronariae in apple leaf samples from the field. In general, our study provided a straightforward and efficient method for rapid diagnosis of apple blotch caused by M. coronariae, which could be applied in field condition and early occurrence of disease caused by M. coronariae could be detected.
Minimal Invasive Versus Open Surgery for Colorectal Liver Metastases: A Multicenter German StuDoQ|Liver Registry-Based Cohort Analysis in Germany
Authors: Moosburner Simon , Kettler Chiara , Hillebrandt Karl H. , Blank Moritz , Freitag Hannes , Knitter Sebastian , Krenzien Felix , Nevermann Nora , Sauer Igor M. , Modest Dominik P. , Lurje Georg , Öllinger Robert , Schöning Wenzel , Werner Jens , Schmeding Maximilian , Pratschke Johann , Raschzok Nathanael ,   members of StuDoQ|Liver of Deutsche Gesellschaft für Allgemein- und Viszeralchirurgie/StuDoQ
Published: November 2023

Objective:

To compare the outcome of minimally invasive liver surgery (MILS) to open liver surgery (OLS) for resection of colorectal liver metastases (CRLM) on a nationwide level.

Background:

Colorectal cancer is the third most common malignancy worldwide. Up to 50% of all patients with colorectal cancer develop CRLM. MILS represents an attractive alternative to OLS for treatment of CRLM.

Methods:

Retrospective cohort study using the prospectively recorded German Quality management registry for liver surgery. Propensity-score matching was performed to account for variance in the extent of resection and patient demographics.

Results:

In total, 1037 patients underwent liver resection for CRLM from 2019 to 2021. MILS was performed in 31%. Operative time was significantly longer in MILS (234 vs 222 minutes, P = 0.02) compared with OLS. After MILS, median length of hospital stay (LOS) was significantly shorter (7 vs 10 days; P < 0.001). Despite 76% of major resections being OLS, postoperative complications and 90-day morbidity and mortality did not differ. The Pringle maneuver was more frequently used in MILS (48% vs 40%, P = 0.048). After propensity-score matching for age, body mass index, Eastern Cooperative Oncology Group, and extent of resection, LOS remained shorter in the MILS cohort (6 vs 10 days, P < 0.001) and operative time did not differ significantly (P = 0.2).

Conclusion:

MILS is not the standard for resection of CRLM in Germany. Drawbacks, such as a longer operative time remain. However, if technically possible, MILS is a reasonable alternative to OLS for resection of CRLM, with comparable postoperative complications, reduced LOS, and equal oncological radicality.
Trauma as a Public Health Moment: Addressing Vaccine Uptake in Trauma Patients
Authors: Keegan Grace E. , Alexander Rachel , Ogunnowo Simi , Brown Isaiah , Zakrison Tanya L. , Hoefer Lea E.
Published: November 2023

Objective:

Our objective was to identify factors associated with COVID-19 vaccination in trauma patients and to provide an opportunity for patients to engage in conversations about vaccination.

Background:

The trauma surgery service offers a unique opportunity to promote preventative health interventions in hard-to-reach populations.

Methods:

Trauma inpatients in Chicago, IL were recruited for this mixed-methods study from February 2022 to April 2022. Participants completed a survey on demographics, COVID-19 vaccination status, and Experiences of Discrimination Scale adapted for medical settings. Differences between vaccinated and unvaccinated patients were analyzed using the Wilcoxon-rank sum test. A semistructured, qualitative interview was completed. Qualitative data was transcribed and analyzed using Grounded Theory Methodology.

Results:

Fifty-eight trauma patients were surveyed, representing 88% of patients approached. Only 23 (40%) patients reported full vaccination to COVID-19. Previous vaccination (at least 1 dose) was associated with greater concern for COVID-19 (OR 3.47, 95% CI 1.987–6.964, P < 0.001) and higher income (OR 1.21, 95% CI 1.02–1.44, P = 0.03). Higher Experiences of Discrimination Scale scores were associated with decreased likelihood of prior vaccination (OR 0.97, 95% CI 0.95–0.99, P = 0.04). On qualitative analysis, recurrent themes included vaccination motivated by either community-based or personal health-related values, and disinterest in vaccination based on perceived low need or skepticism of experimentation. Fifteen patients (26%) eligible for a vaccine dose consented to onsite vaccination after the survey.

Conclusions:

Trauma patients who have experienced more discrimination in medical settings have lower rates of COVID-19 vaccination. Vaccination rates in our population were over 2 times lower than citywide rates, but admission to the trauma service can increase comprehensive care.
Recent advances on neutrophil dysregulation in the pathogenesis of rheumatic diseases
Authors: Chen Jianing , Wang Xinyu , Liu Yudong , Zhang Xuan
Published: November 2023

Purpose of review

The exact pathogenic mechanisms of rheumatic diseases (RMD) remain largely unknown. Increasing evidence highlights a pathogenic role of neutrophil dysregulation in the development of RMD.

Recent findings

The purpose of this review is to present a current overview of recent advancements in understanding the role of neutrophil dysfunction in the development of RMD. Additionally, this review will discuss strategies for targeting pathways associated with neutrophil dysregulation as potential treatments for RMD. One specific aspect of neutrophil dysregulation, known as neutrophil extracellular traps (NETs), will be explored. NETs have been found to contribute to chronic pulmonary inflammation and fibrosis, as well as serve as DNA scaffolds for binding autoantigens, including both citrullinated and carbamylated autoantigens. Putative therapies, such as 6-gingerol or defibrotide, have demonstrated beneficial effects in the treatment of RMD by suppressing NETs formation.

Recent advances have significantly reinforced the crucial role of neutrophil dysregulation in the pathogenesis of RMD. A deeper understanding of the potential mechanisms underlying this pathogenic process would aid in the development of more precise and effective targeting strategies, thus ultimately improving the outcomes of RMD.
Patient-reported outcomes of adolescents with tibia shaft fractures: comparison of closed reduction and casting vs. elastic stable intramedullary nailing
Authors: Torres-Izquierdo Beltran , Tippabhatla Abhishek , Pereira Daniel E. , Cummings Jason L. , Rivera Asdrubal E. , Meyer Zachary I. , Hosseinzadeh Pooya
Published: November 2023

Tibial shaft fractures are the third most common pediatric long bone fractures. Closed reduction and casting (CRC) is considered initial treatment in this population, however, surgical management using elastic stable intramedullary nailing (ESIN) is also used in adolescents. This study compared patient-reported outcomes in a cohort of adolescents with tibia fractures treated with ESIN or CRC. This single-center retrospective study gathered adolescent patients 10–18 years of age with closed tibia shaft fractures between the years 2015 and 2021 treated by either CRC or ESIN. Measured outcomes include patient demographics, overall casting time, time to full weight bearing, time to full healing, radiographic healing, complications (loss of reduction, malunion >5° and >10°) and Patient-Reported Outcomes Measurement Information System (PROMIS) scores. A total of 141 patients (68% male) were included, with 31 receiving ESIN and 110 having CRC. Patient demographics were similar across groups. At follow-up, CRC had a significant shorter time to healing (11 vs. 15 weeks), but an increased casting duration (7 vs. 4 weeks). Finally, the ESIN group had significantly greater pre-intervention angulation, displacement, and shortening. In both interventions, mobility and pain interference scores showed significant improvements from baseline (2 weeks post-op) at 12, 16, and 24 weeks. No statistically significant differences were noted between CRC and ESIN groups across PROMIS domains of pain interference and mobility. CRC and ESIN are effective in improving pain and mobility in adolescent diaphyseal tibia fractures, but neither intervention is superior based on PROMIS scores at 12, 16 and 24+ weeks. From a patient standpoint, we demonstrate that neither treatment is superior in achieving better-perceived mobility or decreasing pain sooner. Level of Evidence: Level III.
Do Pedicle Screws That Terminate in the Costovertebral Joint Compromise Proximal Anchor Fixation in a Dual Growing Rod Construct?
Authors: Henstenburg Jeffrey , Hori Yusuke , Rogers Kenneth J. , Petfield Joseph L. , Shah Suken A. , Gabos Peter G.
Published: November 2023

Introduction:

Growing rods (GRs) are used to treat early-onset scoliosis (EOS) recalcitrant to bracing and casting. Proximal anchor pullout, a known complication of GR constructs, can result in spinal cord injury if pedicle screw anchors are placed with a lateral-to-medial trajectory. To mitigate this risk, a more straightforward and potentially safer trajectory may result in screws that terminate within the costovertebral joint (CVJ). We asked, how often does CVJ placement occur and does this technique increase the rate of failure in GR constructs?

Methods:

We retrospectively reviewed 35 patients with EOS treated with dual GR with >2-year follow-up excluding patients with skeletal dysplasia or history of previous posterior instrumentation. Patient demographics, radiographic parameters, and implant constructs were assessed.

Results:

Of patients meeting the inclusion criteria, 18/35 (51%) were females with an average age of 7.96 (range: 4.0 to 15.2) years at surgery with a follow-up of 3.7 (range: 2.0 to 7.7) years. Five (14%) patients had idiopathic EOS, 5 (14%) had congenital EOS, 12 (34%) had neuromuscular EOS, 10 (29%) had syndromic scoliosis, and 3 (9%) had another etiology for EOS. Among 195 proximal pedicle screws placed, 19 (10%) terminated within the CVJ, and 13 patients (37%) had at least 1 CVJ screw. Two patients (6%) experienced unilateral proximal pullout. In both patients, the anchors on the affected side included 1 of 2 screws within the CVJ. Both patients had constructs that included 2 screws on the side that pulled out and 3 screws on the side that did not. None of the remaining 17 CVJ screws led to implant failure.

Conclusion:

Pedicle screw placement within the CVJ is common and does not appear to significantly contribute to proximal screw pullout; however, it may contribute to unilateral implant failure in constructs employing only 2 proximal screws, where 1 of those 2 screws terminates within the CVJ. Construct modifications should be considered in this scenario.

Level of Evidence:

Level III.
Etiology-independent activation of the LTβ-LTβR-RELB axis drives aggressiveness and predicts poor prognosis in HCC
Authors: Scherr Anna-Lena , Nader Luisa , Xu Kaiyu , Elssner Christin , Ridder Dirk A. , Nichetti Federico , Mastel Manuel , Fritzsche Sarah , Kelmendi Eblina , Schmitt Nathalie , Hoffmeister-Wittmann Paula , Weiler Sofia M. E. , Korell Felix , Albrecht Thomas , Schwab Maximilian , Isele Hanna , Kessler Annika , Hüllein Jennifer , Seretny Agnieszka , Ye Liangtao , Urbanik Toni , Welte Stefan , Leblond Anne-Laure , Heilig Christoph E. , Rahbari Mohammad , Ali Adnan , Gallage Suchira , Lenoir Bénédicte , Wilhelm Nina , Gärtner Ulrike , Ogrodnik Simon J. , Springfeld Christoph , Tschaharganeh Darjus , Fröhling Stefan , Longerich Thomas , Schulze-Bergkamen Henning , Jäger Dirk , Brandl Lydia , Schirmacher Peter , Straub Beate K. , Weber Achim , De Toni Enrico N. , Goeppert Benjamin , Heikenwalder Mathias , Jackstadt Rene , Roessler Stephanie , Breuhahn Kai , Köhler Bruno C.
Published: November 2023

Background and Aims:

HCC is the most common primary liver tumor, with an increasing incidence worldwide. HCC is a heterogeneous malignancy and usually develops in a chronically injured liver. The NF-κB signaling network consists of a canonical and a noncanonical branch. Activation of canonical NF-κB in HCC is documented. However, a functional and clinically relevant role of noncanonical NF-κB and its downstream effectors is not established.

Approach and Results:

Four human HCC cohorts (total n = 1462) and 4 mouse HCC models were assessed for expression and localization of NF-κB signaling components and activating ligands. In vitro, NF-κB signaling, proliferation, and cell death were measured, proving a pro-proliferative role of v-rel avian reticuloendotheliosis viral oncogene homolog B (RELB) activated by means of NF-κB-inducing kinase. In vivo, lymphotoxin beta was identified as the predominant inducer of RELB activation. Importantly, hepatocyte-specific RELB knockout in a murine HCC model led to a lower incidence compared to controls and lower maximal tumor diameters. In silico, RELB activity and RELB-directed transcriptomics were validated on the The Cancer Genome Atlas HCC cohort using inferred protein activity and Gene Set Enrichment Analysis. In RELB-active HCC, pathways mediating proliferation were significantly activated. In contrast to v-rel avian reticuloendotheliosis viral oncogene homolog A, nuclear enrichment of noncanonical RELB expression identified patients with a poor prognosis in an etiology-independent manner. Moreover, RELB activation was associated with malignant features metastasis and recurrence.

Conclusions:

This study demonstrates a prognostically relevant, etiology-independent, and cross-species consistent activation of a lymphotoxin beta/LTβR/RELB axis in hepatocarcinogenesis. These observations may harbor broad implications for HCC, including possible clinical exploitation.
Ultrathin nonectatic cornea with normal slit‐scanning and Scheimpflug-based tomographic findings with suspicious corneal biomechanical properties
Authors: Nagy Khaled , Elshorbagy Sameh , Eldorghamy Alaa , Mounir Amr
Published: November 2023

A 30-year-old man complained of bilateral defective vision due to bilateral refractive error. The uncorrected distance visual acuity (UDVA) in the right eye was 0.06, with corrected distance visual acuity (CDVA) to 1.00 by a refraction of −2.50 × −2.75 × 15, whereas the UDVA in the left eye was 0.05, with CDVA to 0.80 by a refraction of −4.75 × −2.50 × 64. Corneal tomography was performed for both eyes and showed normal corneal tomography with symmetrical bowtie, but the thinnest pachymetry was extremely low. Corneal tomography examination together with Scheimpflug-based tomography was performed after 1 year and the results were the same. Evaluation of corneal biomechanical properties was performed using corneal visualization Scheimpflug technology. It showed suspicious results, which were mainly explained by this extremely low corneal pachymetry.
The 8-ball surprise
Authors: Nenning Magdalena , Hirnschall Nino , Findl Oliver
Published: November 2023

A rare case of total aniridia and vitreous hemorrhage 2 months after intraocular lens (IOL) exchange through a 6.0 mm limbal incision using a scleral fixation technique in a patient denying any trauma is presented. Extrusion of iris tissue in pseudophakic patients has been reported before, usually associated with globe rupture or dehiscence of corneal or scleral wounds, but to the authors’ knowledge, this is the first reported case of complete iridodialysis occurring after implantation of a scleral-fixated IOL with no obvious history of trauma. The uprooting mechanism of the iris and its disappearance from the eye are discussed.
Surgical methods of total thyroidectomy for differentiated thyroid cancer: A systematic review and Bayesian network meta-analysis
Authors: Yuan Yuquan , Pan Bin , Tang Enjie , Mo Hongbiao , Zhu Junping , Yi Ziying , Lu Dengwei , Yin Tingjie , Sun Yiceng , Yin Supeng , Yang Zeyu , Zhang Fan
Published: November 2023

Background:

Emerging remote-access surgical methods are utilized to treat differentiated thyroid cancer. The study aimed to compare the surgical integrity, safety, efficacy, and postoperative experience of patients among common surgical methods.

Methods:

PubMed, Medline, Cochrane Library, Web of Science, and EMBASE databases were searched from their inception until March 2023. Pairwise meta-analysis and Bayesian network meta-analysis were performed. The surface under the cumulative ranking curve (SUCRA) was used to illuminate the probability that each method would be the best for each outcome.

Results:

Thirty-two studies comprising 7042 patients were included. Robotic bilateral axillo-breast approach (RBABA) and robotic gasless transaxillary approach (RGAA) retrieved fewer lymph nodes (LNs) than open thyroidectomy (OT). RBABA showed a significantly lower permanent recurrent laryngeal nerve (RLN) palsy rate than OT. According to SUCRA values, endoscopic transoral approach (EOA) ranked the highest in retrieved LNs (0.84), the proportion of stimulated serum thyroglobulin < 1.0 ng/mL (0.77), and the pain score (0.77). Endoscopic bilateral areola approach (EBAA) ranked the highest in the transient RLN palsy rate (0.72). Endoscopic gasless transaxillary approach (EGAA) ranked the highest in the transient hypoparathyroidism rate (0.78). RBABA ranked the highest in the rate of permanent RLN palsy (0.94) and hypoparathyroidism (0.77). OT ranked the highest in operative time (0.92).

Conclusions:

Each surgical method of total thyroidectomy has benefits and limitations. EOA performed the best in maintaining surgical integrality and reducing the pain score, while taking a long operative time. Generally, RBABA showed the best advantage in protecting parathyroid glands and RLN but with the longest operative time. OT had the best advantage in operative time. Therefore, OT and EOA are ideal methods for patients with a higher risk of central LN metastasis. RBABA and EOA may not be suitable for elderly patients or those with high anesthesia risk.
Long-term outcomes of surgical interventions for stress urinary incontinence: A systematic review and network meta-analysis
Authors: Chen Yuanzhuo , Zhang Chi , Yang Shiqin , Chen Jiawei , Peng Liao , Chen Jie , Shen Hong , Luo Deyi
Published: November 2023

Background:

Stress urinary incontinence (SUI) is common among women, and surgical interventions have significantly improved patients’ symptoms. The long-term effectiveness of these surgeries is increasingly drawing attention, yet it remains sparsely documented in the literature.

Objective:

To compare the long-term effectiveness and safety of retropubic tension-free vaginal tape (TVT-RP), tension-free vaginal tape-obturator (TVT-O), transobturator tape (TOT), single-incision sling (SIS), Burch colposuspension, and pubovaginal sling (PVS).

Methods:

A comprehensive and systematic literature review was conducted in PubMed, EMBASE, MEDLINE, Cochrane Library, Medicine, and clinicaltrials.gov from inception to May 2023. Selected trials were evaluated for potential bias using the Cochrane tool. Treatment modalities were compared using network meta-analysis to assess objective success rate, subjective success rate, and complications as outcomes.

Results:

A total of 37 studies involving 5,720 patients were included. No significant statistical differences were found among the interventions regarding objective success rate. PVS had the highest surface under the cumulative ranking curve SUCRA value (93.1). For subjective success rate, TVT-RP, TVT-O, and PVS demonstrated superiority over SIS, with PVS having the highest SUCRA value (80.1). SIS had lower overall complication and pain rates compared to other methods, with statistical significance. There were no differences in reoperation rate, exposure rate, and urinary tract infection occurrence among the surgical approaches.

Conclusions:

In terms of long-term effectiveness and safety, TVT-RP and TVT-O appear to be the preferred options for patients opting for synthetic slings, while for patients seeking non-synthetic slings, PVS may represent the optimal choice.
Metabolic syndrome and surgical complications: A systematic review and meta-analysis of 13 million individuals
Authors: Norris Philip , Gow Jeff , Arthur Thomas , Conway Aaron , Fleming Fergal J , Ralph Nicholas
Published: November 2023

Background:

Metabolic syndrome is characterised by the presence of at least three of the five following components: insulin resistance, obesity, chronic hypertension, elevated serum triglycerides and decreased high-density lipoprotein cholesterol concentrations. It is estimated to affect 1 in 3 people around the globe and reported to affect 46% of surgical patients. For people with metabolic syndrome who undergo surgery, an emerging body of literature points to significantly poorer postoperative outcomes compared with non-affected populations. The aim of this study is to review the current evidence on risks of surgical complications in patients with metabolic syndrome compared to those without metabolic syndrome.

Methods:

Systematic review and meta-analysis using PRISMA and AMSTAR reporting guidelines.

Results:

The meta-analysis included 63 studies involving 1,919,347 patients with metabolic syndrome and 11,248,114 patients without metabolic syndrome. Compared to individuals without the condition, individuals with metabolic syndrome were at an increased risk of mortality (OR 1.75 95% CIs [1.36-2.24]; P <0.01); all surgical site infection types as well as dehiscence (OR 1.64 95% CIs [1.52 -1.77]; P <0.01); cardiovascular complications (OR 1.56 95% CIs [1.41 -1.73]; P <0.01) including myocardial infarction, stroke, cardiac arrest, cardiac arrythmias and deep vein thrombosis; increased length of hospital stay (MD 0.65 95% CIs [0.39-0.9]; P <0.01); and hospital readmission (OR 1.55 95% CIs [1.41-1.71]; P <0.01).

Conclusion:

Metabolic syndrome is associated with a significantly increased risk of surgical complications including mortality, surgical site infection, cardiovascular complications, increased length of stay and hospital readmission. Despite these risks and the high prevalence of metabolic syndrome in surgical populations there is a lack of evidence on interventions for reducing surgical complications in patients with metabolic syndrome. The authors suggest prioritising interventions across the surgical continuum that include (1) preoperative screening for metabolic syndrome; (2) surgical prehabilitation; (3) intraoperative monitoring and management; and (4) postoperative rehabilitation and follow-up.
Treating Homeless People With Psychiatric Disorders
Authors: Casavola Vita , Giampieri Emanuela , Paggi Elisabetta , Scialò Chiara , Possenti Consuelo , Stefano Bianchi , Lorusso Ottavia , di Giacomo Ester , Clerici Massimo
Published: November 2023

The aim of the “Diogene Project” is to recruit, evaluate, and treat homeless people affected by psychiatric disorders. Three multidisciplinary street units patrolled the streets in Milan, Italy, two/three evenings per week to recruit participants. A sociodemographic questionnaire, the HoNOS, and the GAF were administered at recruitment (T0), 1 year (T1), and 2 years (T2) after the first evaluation. Personalized treatment (none, social support, psychiatric treatment + social support) was tailored to each patient's needs. One hundred twelve homeless people participated. Forty-six users dropped out after the first assessment. The highest percentage of dropouts was registered among those who did not receive any kind of treatment (67.4%). Time spent on the street was not significantly correlated to adherence and outcome. Interestingly, the greatest improvement in psychopathological symptoms was recorded among patients under both treatments. This study confirms the validity of our model in approaching such vulnerable patients through specific interventions.
Complex Posttraumatic Stress Disorder and a Biopsychosocial Model of Borderline Personality Disorder
Authors: Paris Joel
Published: November 2023

This review offers a critique of recent attempts to reconceptualize some cases of borderline personality disorder (BPD) within the newer diagnosis of complex posttraumatic stress disorder (CPTSD). The CPTSD construct focuses on the role of childhood trauma in shaping relational problems in adulthood, difficulties that have been previously seen as features of a personality disorder. The CPTSD model fails to consider the role of heritable personality traits, as well as a broader range of psychosocial risk factors. This review proposes that a biopsychosocial model of BPD is more comprehensive, taking into account a wider range of risk factors, while viewing BPD as rooted in gene-environment interactions. In this model, heritable traits are amplified by an adverse psychosocial environment. One can acknowledge the role of trauma as a risk factor without assuming that it fully accounts for the development of personality pathology.
Randomized Controlled Trial of Effects of Behavioral Weight Loss Treatment on Food Cue Reactivity
Authors: Chao Ariana M. , Wadden Thomas A. , Cao Wen , Zhou Yingjie , Maldonado Delphina , Cardel Michelle I. , Foster Gary D. , Loughead James
Published: November 2023

Background

It is not known whether behavioral weight loss can attenuate blood oxygen level-dependent responses to food stimuli.

Objectives

This randomized controlled trial assessed the effects of a commercially available behavioral weight loss program (WW, WeightWatchers) compared to a wait-list control on blood oxygen level-dependent response to food cues.

Methods

Females with obesity (N = 61) were randomized to behavioral weight loss or wait-list control. At baseline and follow-up, participants completed assessments that included functional magnetic resonance imaging scans to assess response to images of high-calorie foods (HCF) or low-calorie foods (LCF), and neutral objects.

Results

There were no significant between-group differences in change from baseline to follow-up in any regions of the brain in response to viewing HCF or LCF. From baseline to follow-up, participants in behavioral weight loss, compared with wait-list control, reported significantly greater increases in desire for LCF. Changes in liking and palatability of LCF and liking, palatability, and desire for HCF did not differ between groups.

Discussion

Behavioral weight loss was associated with increased desire for LCF without changes in neural reactivity to food cues. These results suggest that alteration of neurological processes underlying responsiveness to food is difficult to achieve through behavioral weight management alone.
Depressive Symptoms in Young and Middle-Aged Stroke Patients
Authors: Liu Zhiwei , Zhang Zhenxiang , Wang Jiajia , Ge Song , Zhang Weihong , Xiang Dandan , Liu Qingxuan , Budu Jemima Twumwaah , Lin Beilei , Chen Suyan , Xue Lihong , Mei Yongxia
Published: November 2023

Background

There is heterogeneity in depressive symptoms. However, latent classes of depressive symptoms and the transition and influences of these in young and middle-aged stroke patients are unclear.

Objectives

The aim of this study was to identify the latent classes of depressive symptoms and their transition patterns over time and the influencing factors in young and middle-aged stroke patients from stabilization to 6 months after discharge.

Methods

This is a longitudinal study following the Strengthening the Reporting of Observational Studies in Epidemiology checklist. A total of 272 young and middle-aged stroke participants were recruited from a hospital neurology ward in Henan Province, China. Participants completed a questionnaire on sociodemographic and health information. Latent transition analysis was used to evaluate the transition pattern of latent classes from stabilization to 6 months after discharge and its influencing factors.

Results

One hundred seventy-nine participants were included in the analysis. Three latent classes of depressive symptoms were identified as “mild symptoms,” “grief-sleep-fatigue symptoms,” and “severe symptoms.” Most participants remained in the original latent class from stabilization to 6 months after discharge (probability of 83.8%, 83.8%, and 88.8%). From 3 to 6 months after discharge, the participants with fewer complications were more likely to transition into the mild symptom class.

Discussion

The findings indicate that from stabilization to 6 months after discharge, depressive symptoms in young and middle-aged stroke patients in China transitioned gradually from the severe symptom class to the mild symptom. Patients with fewer numbers of poststroke complications were more likely to transition to the mild symptoms class. Future research should focus on depressive symptoms in early-stage stroke patients and provide sufficient psychological support to patients with a high number of complications.
A Clinical Model to Predict the Occurrence of Select High-risk Infections in the First Year Following Heart Transplantation
Authors: Perry Whitney A. , Chow Jennifer K. , Nelson Jason , Kent David M. , Snydman David R.
Published: November 2023

Background.

Invasive infection remains a dangerous complication of heart transplantation (HT). No objectively defined set of clinical risk factors has been established to reliably predict infection in HT. The aim of this study was to develop a clinical prediction model for use at 1 mo post-HT to predict serious infection by 1 y.

Methods.

A retrospective cohort study of HT recipients (2000–2018) was performed. The composite endpoint included cytomegalovirus (CMV), herpes simplex or varicella zoster virus infection, blood stream infection, invasive fungal, or nocardial infection occurring 1 mo to 1 y post-HT. A least absolute shrinkage and selection operator regression model was constructed using 10 candidate variables. A concordance statistic, calibration curve, and mean calibration error were calculated. A scoring system was derived for ease of clinical application.

Results.

Three hundred seventy-five patients were analyzed; 93 patients experienced an outcome event. All variables remained in the final model: aged 55 y or above, history of diabetes, need for renal replacement therapy in first month, CMV risk derived from donor and recipient serology, use of induction and/or early lymphodepleting therapy in the first month, use of trimethoprim-sulfamethoxazole prophylaxis at 1 mo, lymphocyte count under 0.75 × 103cells/µL at 1 mo, and inpatient status at 1 mo. Good discrimination (C-index 0.80) and calibration (mean absolute calibration error 3.6%) were demonstrated.

Conclusion.

This model synthesizes multiple highly relevant clinical parameters, available at 1 mo post-HT, into a unified, objective, and clinically useful prediction tool for occurrence of serious infection by 1 y post-HT.
Therapeutic Donor Kidney Transplant Outcomes: Comparing Early US Experiences Using Optimal Matching
Authors: Yamauchi Junji , Raghavan Divya , Rofaiel George , Zimmerman Michael , Potluri Vishnu S. , Baker Talia , Campsen Jeffrey , Hall Isaac E. , Molnar Miklos Z.
Published: November 2023

Background.

Therapeutic donors (TDs) are individuals who undergo organ removal for medical treatment with no replacement organ, and the organ is then transplanted into another person. Transplant centers in the United States have started using TDs for kidney transplantation (KT). TD-KT recipient outcomes may be inferior to those of non-TD-living-donor (non-TD-LD)-KT or deceased-donor (DD)-KT because of the conditions that led to nephrectomy; however, these outcomes have not been sufficiently evaluated.

Methods.

This was a retrospective cohort study using Organ Procurement and Transplantation Network data. Via optimal matching methods, we created 1:4 fivesomes with highly similar characteristics for TD-KT and non-TD-LD-KT recipients and then separately for TD-KT and DD-KT recipients. We compared a 6-mo estimated glomerular filtration rate (eGFR) between groups (primary endpoint) and a composite of death, graft loss, or eGFR <30 mL/min/1.73 m2 at 6 mo (secondary).

Results.

We identified 36 TD-KT recipients with 6-mo eGFR. There was also 1 death and 2 graft losses within 6 mo. Mean ± SD 6-mo eGFR was not significantly different between TD-KT, non-TD-LD-KT, and DD-KT recipients (59.9 ± 20.7, 63.3 ± 17.9, and 59.9 ± 23.0 mL/min/1.73 m2, respectively; P > 0.05). However, the 6-mo composite outcome occurred more frequently with TD-KT than with non-TD-LD-KT and DD-KT (18%, 2% [P < 0.001], and 8% [P = 0.053], respectively).

Conclusions.

Early graft function was no different between well-matched groups, but TD-KT demonstrated a higher risk of otherwise poor 6-mo outcomes compared with non-TD-LD-KT and DD-KT. Our results support selective utilization of TD kidneys; however, additional studies are needed with more detailed TD kidney information to understand how to best utilize these kidneys.
Oncogenic RAS-Pathway Activation Drives Oncofetal Reprogramming and Creates Therapeutic Vulnerabilities in Juvenile Myelomonocytic Leukemia
Authors: Hartmann Mark , Schönung Maximilian , Rajak Jovana , Maurer Valentin , Hai Ling , Bauer Katharina , Hakobyan Mariam , Staeble Sina , Langstein Jens , Jardine Laura , Rölz Roland , Bohler Sheila , Khabirova Eleonora , Maag Abdul-Habib , Vonficht Dominik , Lebrecht Dirk , Bernt Katrin M. , Tan Kai , Chen Changya , Alikarami Fatemeh , Boch Tobias , Flore Viktoria , Lutsik Pavlo , Milsom Michael D. , Raffel Simon , Buske Christian , Haas Simon , Haniffa Muzlifah , Mallm Jan-Philipp , Behjati Sam , Bonder Marc-Jan , Fröhling Stefan , Niemeyer Charlotte M. , Hey Joschka , Flotho Christian , Plass Christoph , Erlacher Miriam , Schlesner Matthias , Lipka Daniel B.
Published: November 2023

Aberrant fetal gene expression facilitates tumor-specific cellular plasticity by hijacking molecular programs of embryogenesis1. Persistent fetal gene signatures in childhood malignancies are typically explained by their prenatal origins2–6. In contrast, reactivation of fetal gene expression is considered a consequence of oncofetal reprogramming (OFR) in adult malignancies and is associated with aggressive disease7–10. To date, OFR has not been described in the context of childhood malignancies. Here, we performed a comprehensive multi-layered molecular characterization of juvenile myelomonocytic leukemia (JMML) and identified OFR as a hallmark of aggressive JMML. We observed that hematopoietic stem cells (HSCs) aberrantly express mixed developmental programs in JMML. Expression of fetal gene signatures combined with a postnatal epigenetic landscape suggested OFR, which was validated in a JMML mouse model, demonstrating that postnatal activation of RAS signaling is sufficient to induce fetal gene signatures. Integrative analysis identified the fetal HSC maturation marker CD52 as a novel therapeutic target for aggressive JMML. Anti-CD52 treatment depleted human JMML HSCs and disrupted disease propagationin vivo. In summary, this study implicates OFR, defined as postnatal acquisition of fetal transcription signatures, in the pathobiology of a childhood malignancy. We provide evidence for the direct involvement of oncogenic RAS signaling in OFR. Finally, we demonstrate how OFR can be leveraged for the development of novel treatment strategies.

Highlights

▪ Epigenomic and transcriptomic landscape of juvenile myelomonocytic leukemia (JMML) in the context of hematopoietic development.

▪ The presence of fetal transcription signatures in childhood malignancies is not indicative of a developmental maturation block.

▪ High-risk JMML is characterized by oncofetal reprogramming of postnatal hematopoietic stem cells (HSCs).

▪ RAS-pathway mutations induce fetal-like gene expression signatures in murine postnatal HSCs.

▪ The fetal maturation marker CD52 is a novel therapeutic target in high-risk JMML.