Cross-species modeling of plant genomes at single nucleotide resolution using a pre-trained DNA language model.

Understanding the function and fitness effects of diverse plant genomes requires transferable models. Language models (LMs) pre-trained on large-scale biological sequences can learn evolutionary conservation, thus expected to offer better cross-species prediction through fine-tuning on limited labeled data compared to supervised deep learning models. We introduce PlantCaduceus, a plant DNA LM based on the Caduceus and Mamba architectures, pre-trained on a carefully curated dataset consisting of 16 diverse Angiosperm genomes. Fine-tuning PlantCaduceus on limited labeled Arabidopsis data for four tasks involving transcription and translation modeling demonstrated high transferability to maize that diverged 160 million years ago, outperforming the best baseline model by 1.45-fold to 7.23-fold. PlantCaduceus also enables genome-wide deleterious mutation identification without multiple sequence alignment (MSA). PlantCaduceus demonstrated a threefold enrichment of rare alleles in prioritized deleterious mutations compared to MSA-based methods and matched state-of-the-art protein LMs. PlantCaduceus is a versatile pre-trained DNA LM expected to accelerate plant genomics and crop breeding applications.

The butterfly effect on glioblastoma: is volumetric extent of resection more effective than biopsy for these tumors?

A subset of patients with glioblastoma (GBM) have butterfly GBM (bGBM) that involve both cerebral hemispheres by crossing the corpus callosum. The prognoses, as well as the effectiveness of surgery and adjuvant therapy, are unclear because studies are few and limited. The goals of this study were to: (1) determine if bGBM have worse outcomes than patients with non-bGBM, (2) determine if surgery is more effective than biopsy, and (3) identify factors independently associated with improved outcomes for these patients. Adult patients who underwent surgery for a newly diagnosed primary GBM at an academic tertiary-care institution between 2007 and 2012 were retrospectively reviewed and tumors were volumetrically measured. Of the 336 patients with newly diagnosed GBM who were operated on, 48 (14 %) presented with bGBM, where 29 (60 %) and 19 (40 %) underwent surgical resection and biopsy, respectively. In multivariate analysis, a bGBM was independently associated with poorer survival [HR (95 % CI) 1.848 (1.250-2.685), p < 0.003]. In matched-pair analysis, patients who underwent surgical resection had improved median survival than biopsy patients (7.0 vs. 3.5 months, p = 0.03). In multivariate analysis, increasing percent resection [HR (95 % CI) 0.987 (0.977-0.997), p = 0.01], radiation [HR (95 % CI) 0.431 (0.225-0.812), p = 0.009], and temozolomide [HR (95 % CI) 0.413 (0.212-0. 784), p = 0.007] were each independently associated with prolonged survival among patients with bGBM. This present study shows that while patients with bGBM have poorer prognoses compared to non-bGBM, these patients can also benefit from aggressive treatments including debulking surgery, maximal safe surgical resection, temozolomide chemotherapy, and radiation therapy.

Incidence of sacral fractures and in-hospital postoperative complications in the United States: an analysis of 2002-2011 data.

STUDY DESIGN: Retrospective study of an administrative database. OBJECTIVE: To estimate the incidence of sacral fractures in the United States and report short-term outcomes after their surgical management. SUMMARY OF BACKGROUND DATA: The incidence of sacral fractures in the United States is currently unknown, and these lesions have been associated with significant morbidity after their surgical management. METHODS: This study used the Nationwide Inpatient Sample database for the years 2002-2011. All patients with a primary discharge diagnosis of a sacral fracture with and without a neurological injury were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Patients with a diagnosis of osteoporosis or pathological fracture were excluded. A stepwise multivariate logistic regression analysis was performed to identify factors associated with an in-hospital complication. RESULTS: During the study period, 10,177 patients with a nonosteoporotic sacral fracture were identified, of whom 1002 patients underwent surgery. Between 2002 and 2011, the estimated incidence of sacral fractures increased from 0.67 per 100,000 persons to 2.09 (P < 0.001). Similarly, the rate of surgical treatment for sacral fractures increased from 0.05 per 100,000 persons in 2002 to 0.24 per 100,000 in 2011 (P < 0.001). Complications occurred in 25.95% of patients and remained steady over time (P = 0.992). Average length of stay significantly decreased from 11.93 days to 9.66 days in the 10-year period (P = 0.023). The independent factors associated with an in-hospital complication were congestive heart failure (odds ratio, 3.65; 95% confidence interval, 1.18-11.26), coagulopathy (odds ratio, 3.58; 95% confidence interval, 1.88-6.81), and electrolyte abnormalities (odds ratio, 3.28; 95% confidence interval, 2.14-5.02). CONCLUSION: During the examined 10-year period, both the incidence of nonosteoporotic sacral fractures and the surgical treatment of these lesions increased in the United States. Between 2002 and 2011, although patient comorbidity increased, in-hospital complication rates remained stable and length of stay significantly decreased over time. LEVEL OF EVIDENCE: 4.

Spontaneous regression of sequestrated lumbar disc herniations: Literature review.

Lumbar disc herniations (LDH) may regress with conservative management; however, this phenomenon is poorly understood for the sequestrated subtype of LDH. We present one of the first comprehensive literature reviews specifically addressing the spontaneous regression of sequestrated intervertebral discs. We reviewed all publications with lumbar disc herniations, sequestrated subtype. Our results were then narrowed to patients who experienced spontaneous regression of the sequestration. Based on our literature review of 53 cases, patients with sequestrated lumbar disc herniations experienced symptomatic resolution in a mean of 1.33±1.34 months and radiographic resolution in 9.27±13.32 months. Symptomatic patients with sequestrated discs present similarly to those with other types of lumbar disc herniations. Sequestrations may have the highest likelihood to radiographically regress in the shortest time frame in comparison to the remaining subtypes of LDH. The most likely mechanism for regression is an inflammatory response elicited against the free fragment. Patients with disc sequestrations may be managed conservatively, in the absence of intractable pain, inability to walk, weakness or symptoms suggestive of cauda equina syndrome.

Lumbar fusion versus nonoperative management for treatment of discogenic low back pain: a systematic review and meta-analysis of randomized controlled trials.

STUDY DESIGN: Systematic review and meta-analysis of randomized controlled trials (RCTs). OBJECTIVE: To evaluate the current evidence comparing lumbar fusion to nonoperative management for the treatment of chronic discogenic low back pain. BACKGROUND AND CONTEXT: Discogenic low back pain is a common and sometimes disabling condition. When the condition becomes chronic and intractable, spinal fusion may play a role. METHODS: A systematic review of the literature was conducted using the PubMed and CENTRAL databases. We included RCTs that compared lumbar fusion to nonoperative management for the treatment of adult patients with chronic discogenic low back pain. A meta-analysis was conducted to assess the improvement in back pain based on the Oswestry Disability Index (ODI). RESULTS: Five RCTs met our inclusion criteria. A total of 707 patients were divided into lumbar fusion (n=523) and conservative management (n=134). Although inclusion/exclusion criteria were relatively similar across studies, surgical techniques and conservative management protocols varied. The pooled mean difference in ODI (final ODI-initial ODI) between the nonoperative and lumbar fusion groups across all studies was -7.39 points (95% confidence interval: -20.26, 5.47) in favor of lumbar fusion, but this difference was not statistically significant (P=0.26). CONCLUSIONS: Despite the significant improvement in ODI in the lumbar fusion groups in 3 studies, pooled data revealed no significant difference when compared with the nonoperative group. Although there was an overall improvement of 7.39 points in the ODI in favor of lumbar fusion, it is unclear that this change in ODI would lead to a clinically significant difference. Prospective randomized trials comparing a specific surgical technique versus a structured physical therapy program may improve evidence quality. Until then, either operative intervention by lumbar fusion or nonoperative management and physical therapy remain 2 acceptable treatment methods for intractable low back pain.